CN115989007A

CN115989007A - Wrappable bone implant for encapsulating bone material

Info

Publication number: CN115989007A
Application number: CN202180053321.6A
Authority: CN
Inventors: C·S·罗德斯; D·A·施姆科
Original assignee: Warsaw Orthopedic Inc
Current assignee: Warsaw Orthopedic Inc
Priority date: 2020-08-28
Filing date: 2021-08-26
Publication date: 2023-04-18
Also published as: EP4203863A1; WO2022047069A1; US20220062503A1

Abstract

A bone implant (10) for encapsulating bone material (12) is provided. The bone implant includes a covering (18), which may be a biodegradable mesh. The covering is configured to be rolled to a diameter to at least partially encapsulate the bone material within the covering. In some embodiments, the cover includes a body portion (80) and a closure portion (82) adjacent the body portion. The closure portion is configured to hold the covering in a rolled configuration to a predetermined diameter to at least partially encapsulate the bone material. A kit and method of using the bone implant is also provided.

Description

Wrappable bone implant for encapsulating bone material

Background

The use of bone grafts and bone substitute materials in orthopaedic medicine is known. Although bone wounds can regenerate without scar tissue formation, fractures and other orthopedic injuries take a long time to heal, during which time the bone is unable to independently support physiologic loads. Metal pins, screws, rods, plates and meshes are often required to replace the mechanical function of injured bone. However, metal is significantly harder than bone. The use of metal implants may result in a reduction in bone density around the implant site due to stress shielding. Physiological stress and corrosion can lead to fracture of the metal implant. Unlike bone, which can only be replaced or removed, damaged metal implants can heal small damage fractures by remodeling to prevent larger damage and failure. The body's natural cellular healing and remodeling mechanisms coordinate the removal of bone and bone graft by osteoclasts and the formation of osteoblasts.

Conventionally, bone tissue regeneration is achieved by filling a bone repair site with bone graft (e.g., bone material). Over time, the bone graft is bound by the host and new bone remodels the bone graft. For placement of bone grafts, either integrally pre-formed bone grafts or bone implants comprising granular bone formed in a carrier are typically used. Generally, the resulting implant, whether monolithic, or granular and in a carrier, is substantially solid at the time of implantation and therefore does not conform to the implantation site. The implant is also substantially intact at the time of implantation and therefore offers little ability to be customized, for example by adding autografts or changing the shape of the implant.

The use of bone grafts is generally limited by the available shape and size of the graft. Bone grafts are often available pre-shaped and pre-sized. However, many surgeons prefer to utilize the local bone obtained during surgery by combining it with another implant, but cannot do so if the implant is pre-shaped or pre-sized. Patient autografts may be combined with moldable grafts, but these moldable grafts may not be contained and may migrate from the wound site. Furthermore, bone grafts using cortical bone remodel slowly due to their limited porosity. Traditional bone substitute materials remodel faster, but do not immediately provide mechanical support. Furthermore, while bone substitute materials may themselves be used to fill odd-shaped bone defects, such materials are less suitable for use in wrapping bone or repairing bone surfaces.

Accordingly, it would be beneficial to provide a bone implant that can be filled with bone material (e.g., natural bone particles and/or synthetic bone particles), can be easily sized in length and diameter, or can be otherwise adjusted at the point of care for implantation at a variety of surgical sites. A bone implant that can be customized in real-time according to the size and shape of the bone defect in the patient's anatomy and the type of bone material to be used would be desirable. Kits and methods relating to filling and implanting these adjustable bone implants would also be desirable.

Disclosure of Invention

A bone implant is provided that can partially or completely encapsulate bone material and can be easily sealed and implanted at a surgical site. Bone implants may be customized according to the size and shape of the bone defect and the type of bone material to be used. Kits and methods relating to filling and implanting such bone implants are also provided.

In one embodiment, a bone implant for encapsulating bone material is provided. The bone implant includes a covering, which in some aspects is a biodegradable mesh. The covering is configured to be rolled to a diameter to at least partially encapsulate the bone material within the covering.

In another embodiment, a bone implant for encapsulating bone material includes a cover, wherein the cover includes a body portion and a closure portion adjacent the body portion. In some embodiments, the closure portion is configured to hold the covering in a rolled configuration to a predetermined diameter to at least partially encapsulate the bone material.

In one embodiment, a kit for manufacturing a bone implant is provided. The kit includes a bone implant that may be a covering. In many aspects, the covering is configured to be rolled to a diameter to at least partially encapsulate the bone material within the covering. The kit may further comprise at least one of: (i) A plurality of sizing rings or cylinders configured to engage the bone implant to adapt the implant to a desired diameter; or (ii) a funnel of varying diameter configured to load the covering with a quantity of the bone material. In some embodiments, the kit may further comprise a desiccant to prevent hydrolytic degradation during storage.

In another embodiment, a kit for manufacturing a bone implant comprises: a covering, wherein the covering comprises a body portion and a closure portion adjacent the body portion, the closure portion configured to hold the covering in a rolled configuration to a predetermined diameter to at least partially encapsulate bone material; and a binder.

In one embodiment, a method of implanting a bone implant at a surgical site is provided. The method comprises the following steps: providing a bone implant comprising a covering configured to be rolled to a diameter to at least partially encapsulate bone material within the covering; encapsulating the bone material in the covering by adapting the covering to a rolled configuration; and placing the bone implant at the surgical site, thereby implanting the bone implant at the surgical site.

In another embodiment, a method of implanting a bone implant at a surgical site includes: providing a bone implant comprising a cover comprising a body portion and a closure portion adjacent the body portion, the closure portion configured to hold the cover in a rolled configuration to a predetermined diameter to at least partially encapsulate bone material; encapsulating the bone material in the covering by adapting the covering to a rolled configuration; and placing the bone implant at the surgical site, thereby implanting the bone implant at the surgical site.

While multiple embodiments are disclosed, other embodiments of the present application will become apparent to those skilled in the art from the following detailed description, which is to be read in connection with the accompanying drawings. It will be apparent that the disclosure is capable of modification in various obvious respects, all without departing from the spirit and scope of the disclosure. Accordingly, the detailed description is to be regarded as illustrative in nature and not as restrictive.

Drawings

The disclosure will become more apparent from the following detailed description when taken in conjunction with the following drawings.

Fig. 1 shows a perspective view of a bone implant for encapsulating bone material. The bone implant includes a covering that is a mesh configured to be rolled to a diameter to encapsulate bone material within the covering. The bone material is secured within the coiled mesh by strands tied around the coiled mesh that act as closure members.

Fig. 2 shows a perspective view of a bone implant similar to the bone implant of fig. 1 for encapsulating bone material. The bone material is secured by a coiled mesh that is sealed with adhesive at opposite ends and/or at overlaps along the length of the coiled mesh.

Fig. 3 shows a perspective view of a bone implant for encapsulating bone material similar to the bone implant of fig. 2, wherein the bone material is secured by a coiled mesh sealed at opposite ends with sutures (not shown).

Fig. 4A shows a schematic view of a planar covering of a bone implant for encapsulating bone material. The cover has a certain preselected length and width, and has a plurality of strands attached at predetermined intervals on one of the edges of the cover. Once the covering is wrapped around the bone material or graft, the strands may be used to secure the bone material by tying the strands around the wrapped covering. Shown are a plurality of strands disposed on the edges of the cover at spaced distances from each other.

Fig. 4B shows a schematic view of a planar covering of a bone implant for encapsulating bone material similar to the schematic view of fig. 4A. The cover of this figure has different preselected lengths and has a plurality of strands attached at predetermined intervals on one of the edges of the cover that form the length of the cover. Once the covering is wrapped around the bone material or graft, the strands may be used to secure the bone material by tying the strands around the wrapped covering.

Fig. 5A shows a perspective view of the covering in a rolled configuration, the covering shaped as a tube without bone material. The strands around the tube are open.

Figure 5B shows a perspective view of the covering of figure 5A in a wrapped configuration with strands tied around the wrapped covering.

Figure 6 shows a schematic view of a flat cover with strands for fixation of bone material across the width of the cover. The exterior of the covering has visual indicia at predefined intervals to assist the user in resizing the covering to form a rolled covering of a particular diameter.

Fig. 7A shows a perspective view of the mesh in a flat configuration with bone material on the inner surface of the mesh.

Fig. 7B shows a perspective view of the mesh of fig. 7A in a coiled configuration, with bone material encapsulated in the mesh.

Fig. 7C shows a perspective view of the mesh of fig. 7A in a partially coiled configuration, with bone material partially encapsulated in the partially coiled mesh.

Fig. 7D shows a schematic view of a covering (e.g., mesh) wrapped into a large diameter tubular configuration encapsulating bone material. In this embodiment, the diameter of the tube may be reduced by applying opposing pulling forces, indicated by arrows, at the open ends.

Fig. 7E shows a schematic view of a covering wrapped into a small diameter tubular configuration encapsulating bone material. After reducing the diameter of the tube by applying pulling forces opposite to each other as indicated by the arrows in 7D.

Fig. 8A, 8B and 8C illustrate sizing rings of different sizes for controlling the diameter of the covering as selected rings are slid over the outer surface of the rolled covering to allow the covering to have a uniform diameter and size.

Fig. 9A shows a perspective view of different sizes of sizing cylinders that may be used to fill the cover and control the diameter of the cover.

Fig. 9B shows different sized rolled coverings to be filled with bone material by using different sized funnels.

Fig. 10 illustrates a perspective view of a variable diameter funnel that may be used to fill a bone implant (e.g., a covering).

Fig. 11 shows a perspective view of a tray including a bone implant encapsulating bone material secured with a closure member that is a strand tied in a knot to hold a covering (e.g., mesh) in a coiled position and to encapsulate the bone material within the covering.

Fig. 12 shows a schematic view of a planar covering of a bone implant for encapsulating bone material. The cover includes a body portion having a narrower interline spacing and a closure portion having a wider interline spacing.

Fig. 13A is a schematic view of a non-elastic thread for use in the body portion and/or closure portion of the covering shown in fig. 12. Inelastic threads generally have a relatively narrow interline spacing.

Fig. 13B is a schematic view of a non-elastic thread for use in the closure portion of the covering shown in fig. 12. The non-elastic threads are arranged in a sinusoidal pattern to impart elasticity to the structure. The lines typically have a wider inter-line spacing than the body portion.

Fig. 14A shows a schematic view of a planar covering for fixation of bone material. The interior of the covering (e.g., mesh) has visual indicia spaced from each other at predefined intervals to assist the user in resizing the covering to form a rolled covering of a particular diameter, length, and width. The cover may have adhesive at discrete areas of the cover. Here, the adhesive is shown as a strip on the right side of the flat covering that can hold the covering in a rolled configuration and at least partially encapsulate the loaded bone material within the covering.

Fig. 14B is a perspective view of the covering shown in fig. 14A in a rolled configuration, with the adhesive holding the covering in the rolled configuration.

It should be understood that the figures are not drawn to scale. Further, the relationships between objects in the figures may not be to scale, and in fact may have an inverse relationship with respect to size. The drawings are intended to aid in understanding and clarity of construction of each illustrated object, and therefore, some features may be exaggerated to illustrate specific features of the structures.

Detailed Description

Definition of

For the purposes of this specification and the appended claims, unless otherwise indicated, all numbers expressing quantities of ingredients, percentages or proportions of materials, reaction conditions, and other numerical values used in the specification and claims are to be understood as being modified in all instances by the term "about". Similarly, when values are expressed as approximations, by use of the antecedent "about," it will be understood that the value forms another embodiment that is +/-10% of the stated value. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present disclosure. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Also, as used in the specification and including the appended claims, the singular forms "a," "an," and "the" include the plural, and reference to a particular numerical value includes at least that particular value, unless the context clearly dictates otherwise. Ranges can be expressed herein as "about" or "approximately" one particular value, and/or "about" or "approximately" another particular value. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value.

Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the application are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Moreover, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein. For example, a range of "1 to 10" includes any and all subranges between (and including) the minimum value of 1 and the maximum value of 10 (i.e., any and all subranges having a minimum value equal to or greater than 1 and a maximum value of equal to or less than 10, e.g., 5.5 to 10.

As used herein, a bioactive agent or bioactive compound or bioactive material is used interchangeably to refer to a compound or entity that alters, inhibits, activates or otherwise affects a biological or chemical event. For example, bioactive agents may include, but are not limited to, osteogenic or chondrogenic proteins or peptides, anti-AIDS substances, anti-cancer substances, antibiotics, immunosuppressive agents, antiviral substances, enzyme inhibitors, hormones, neurotoxins, opioids, hypnotics, antihistamines, lubricants, sedatives, anticonvulsants, muscle relaxants and anti-Parkinson's disease substances (anti-Parkinson substances), antispasmodics and muscle contractants (including channel blockers), miotics and anticholinergics, antiglaucoma compounds, antiparasitics and/or antiprotozoal compounds, modulators of cell-extracellular matrix interactions (including cell growth inhibitors and anti-adhesion molecules), vasodilators, inhibitors of DNA, RNA or protein synthesis, antihypertensives, analgesics, antipyretics, steroidal and non-steroidal anti-inflammatory agents, anti-angiogenic factors, antisecretory factors, anticoagulants and/or antithrombotic agents, local anesthetics, ocular drugs, prostaglandins, anti-emetics, anti-depressants, and imaging agents. In certain embodiments, the bioactive agent is a drug. The bioactive agent further comprises an RNA, such as siRNA, and an osteoclast stimulating factor. In some embodiments, the bioactive agent may be a factor that stops, removes, or reduces the activity of a bone growth inhibitor. In some embodiments, the bioactive agent is a growth factor, cytokine, extracellular matrix molecule, or a fragment or derivative thereof, e.g., a cell attachment sequence, such as RGD. In some embodiments, the bioactive agent comprises a nutrient including, but not limited to, vitamin a, vitamin D, vitamin E, vitamin K2, isoflavones, milk proteins, caffeine, sugars, or a combination thereof.

As used herein, biocompatible is intended to describe a material that does not induce undesirable long-term effects when administered in vivo.

As used herein, bone refers to cortical, cancellous or cortical-cancellous bone of autologous, allogeneic, xenogeneic or transgenic origin.

As used herein, bone graft refers to any implant made according to embodiments described herein, and thus may include expressions such as bone material and periosteum.

The bone material comprises demineralized bone. As used herein, demineralization refers to any material that is generated by removing mineral material from tissue, such as bone tissue. In certain embodiments, demineralized bone material may be added to the bone void filler. Demineralized bone material described herein includes formulations having less than 5%, 4%, 3%, 2%, or 1% calcium by weight. Partially demineralized bone (e.g., a formulation having greater than 5% calcium by weight but containing less than 100% of the original starting amount of calcium) is also contemplated to be within the scope of the present disclosure. In some embodiments, the partially demineralized bone contains greater than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the original starting amount of calcium preparation. In some embodiments, the demineralized bone has less than 95% of its original mineral content. In some embodiments, the demineralized bone has less than 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, or 5% of its original mineral content. Demineralization is intended to encompass such expressions as "substantially demineralization", "partial demineralization", "shallow demineralization", and "complete demineralization". In some embodiments, part or all of the surface of the bone may be demineralized. For example, some or all of the surface of the bone material may be demineralized to a depth of about 100 microns to about 5000 microns, or about 150 microns to about 1000 microns. In some embodiments of the present invention, the substrate is, some or all of the surface of the bone material may be demineralized to a depth of about 100 microns, 150 microns, 200 microns, 250 microns, 300 microns, 350 microns, 400 microns, 450 microns, 500 microns, 550 microns, 600 microns, 650 microns, 700 microns, 750 microns, 800 microns, 850 microns, 900 microns, 950 microns, 1000 microns, 1050 microns, 1100 microns, 1150 microns, 1200 microns, 1250 microns, 1300 microns, 1350 microns, 1400 microns, 1450 microns, 1500 microns, 1550 microns, 1600 microns, 1650 microns, 1700 microns, 1750 microns, 1800 microns, 1850 microns, 1900 microns, 1950 microns, 2000 microns, 2050 microns, 2100 microns, 2150 microns, 2200 microns, 2250 microns, 2300 microns, 2350 microns, 2450 microns, 2400 microns, 2500 microns 2550 microns, 2600 microns, 2650 microns, 2700 microns, 2750 microns, 2800 microns, 2850 microns, 2900 microns, 2950 microns, 3000 microns, 3050 microns, 3100 microns, 3150 microns, 3200 microns, 3250 microns, 3300 microns, 3350 microns, 3400 microns, 3450 microns, 3500 microns, 3550 microns, 3600 microns, 3650 microns, 3700 microns, 3750 microns, 3800 microns, 3850 microns, 3900 microns, 3950 microns, 4000 microns, 4050 microns, 4100 microns, 4150 microns, 4200 microns, 4250 microns, 4300 microns, 4350 microns, 4400 microns, 4450 microns, 4500 microns, 4550 microns, 4600 microns, 4650 microns, 4700 microns, 4750 microns, 4800 microns, 4850 microns, 4900 microns, 4950 microns to a depth of about 5000 microns. Optionally, the bone material may include demineralized material.

Partially demineralized bone refers to a formulation having a calcium content greater than 5% by weight but less than 100% of the original starting amount. In some embodiments, partially demineralized bone comprises 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, and/or 99% of the original initial amount of calcium.

In some embodiments, demineralized bone may be about 1 to 99% surface demineralized. In some embodiments, demineralized bone is 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, and/or 99% demineralized surface. In various embodiments, demineralized bone may be about 15-25% surface demineralized. In some embodiments, demineralized bone is 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, and/or 25% surface demineralized.

As used herein, demineralized Bone Matrix (DBM) refers to any material produced by removing minerals from bone tissue. In some embodiments, DBM compositions for use herein include formulations that contain less than 5% calcium, and in some embodiments, less than 1% calcium by weight. In some embodiments, the DBM composition comprises a formulation comprising less than 5%, 4%, 3%, 2%, and/or 1% calcium by weight. In other embodiments, the DBM composition comprises partially demineralized bone (e.g., a formulation having greater than 5% calcium by weight but containing less than 100% of the original starting amount of calcium).

As used herein, osteoinductive refers to the ability of a substance to act as a template or substance along which bone can grow.

As used herein, osteogenesis refers to a material containing living cells capable of differentiating into osteogenic tissue.

Osteoinductive, as used herein, refers to the property of being able to recruit cells from a host that have the potential to stimulate new bone formation. Any material that induces the formation of ectopic bone in animal soft tissue is considered osteoinductive. For example, most osteoinductive materials induce bone formation in athymic rats when measured according to the following method: edwards et al, "osteoinduction of human demineralized bone: characterization in Rat Model (Osteoinduction of Human refined Bone: characterization in a Rat Model), "Clinical orthopedics and related research (Clinical Orthopaedics & Rel. Res.), (357) 219-228, 12 months 1998, which is incorporated herein by reference.

As used herein, surface demineralization refers to bone-derived elements that have at least about 90% by weight of their original inorganic mineral content. In some embodiments, the surface demineralization contains at least about 90 wt.%, 91 wt.%, 92 wt.%, 93 wt.%, 94 wt.%, 95 wt.%, 96 wt.%, 97 wt.%, 98 wt.%, and/or 99 wt.% of its original inorganic material. As used herein, the expression "fully demineralized" means that bone contains less than 8% of its original mineral content. In some embodiments, the complete demineralization contains about less than 8%, 7%, 6%, 5%, 4%, 3%, 2% and/or 1% of its original mineral content.

The expression "average length to average thickness ratio" as applied to DBM fibers in the present application refers to the ratio of the longest average dimension (average length) of the fiber to its shortest average dimension (average thickness). This is also referred to as the "aspect ratio" of the fiber.

As used herein, fibrous refers to a bone element having a fiber with an average length to average thickness or aspect ratio of about 50. In some embodiments, the fiber has an average length to average thickness or aspect ratio of about 50. The fibrous bone elements may be described as bone fibers, threads, strips or sheets in overall appearance. Generally, when the flakes are produced, their edges tend to curl toward each other. The fibrous bone element may be substantially linear in appearance, or it may be wound to resemble a spring. In some embodiments, the bone fibers have an irregular shape, including, for example, a linear, serpentine, or curved shape. The bone fibers are demineralized, however some of the original mineral content may be retained when required by a particular embodiment. In various embodiments, the bone fibers are mineralized. In some embodiments, the fibers are a combination of demineralization and mineralization.

As used herein, non-fibrous refers to elements having an average width substantially greater than the average thickness or aspect ratio of the fibrous bone element of less than about 50. The non-fibrous bone elements are shaped in a substantially regular manner or in a specific configuration, such as triangular prisms, spheres, cubes, cylinders and other regular shapes. In contrast, particles such as chips, crumbs or powder have an irregular or random geometry. It should be understood that some variation in size may occur in the manufacture of the elements of the present application, and elements exhibiting such variation in size are within the scope of the present application and are intended herein to be understood as being within the boundaries established by the expressions "substantially irregular" and "substantially regular".

As used herein, a wound cover refers to a cover (e.g., a mesh) that is wound by rotating or turning along its length or width until it is in a cylindrical or substantially cylindrical shape.

The term "at least partially encapsulate" means that the covering partially encapsulates the bone material. In some embodiments, the covering will have an open end to partially encapsulate the bone material. These ends may be sewn, sealed or otherwise closed.

Bone implants, devices, kits, and methods can be used to treat spinal disorders such as, for example, degenerative disc disease, disc herniation, osteoporosis, spondylolisthesis, stenosis, scoliosis and other curvature abnormalities, kyphosis, tumors, and fractures. The bone implants, devices, kits and methods can be used for other bone and bone-related applications, including those associated with diagnosis and treatment. It may also be used as an alternative to surgical treatment, where the patient is in a prone or supine position, and/or various surgical approaches are taken to the spine and in other body regions, including anterior, dorsal midline, antero-lateral, posterior and/or anterior approaches. The bone implants, devices, kits and methods can also be used alternatively with procedures for treating the lumbar, cervical, thoracic, sacral and pelvic regions of the spine. It can also be used on animals, bone models and other inanimate substrates, for example in training, testing and demonstration.

In various embodiments, the bone implant comprises a biodegradable mesh comprising poly (lactide-co-glycolide) (PLGA), polylactide (PLA), polyglycolide (PGA), D-lactide, D, L-lactide, D, L-lactide-co-epsilon-caprolactone, D, L-lactide-co-glycolide-co-epsilon-caprolactone, L-lactide-co-epsilon-caprolactone or a combination thereof. In some embodiments, the mesh comprises a bone material, such as, for example, hydroxyapatite, calcium phosphate, a ceramic, or a combination thereof. Bone material, such as hydroxyapatite, calcium phosphate, ceramic, or a combination thereof, may be part of the thread or yarn of the covering, or may be loaded into the covering in particulate form and then encapsulated by the covering.

Bone implant

Referring to fig. 1-3, 4A, 4B, 5A, 5B, and 6, a bone implant 10 is provided that is customizable and configured to encapsulate bone material 12. Bone material 12 may be completely or at least partially encapsulated by covering 18. The bone implant is configured to be cut and shaped to any size and diameter as required for a particular surgical site to match the patient anatomy. Accordingly, customizable coverings are useful for a wide variety of spinal fusion procedures, as well as other applications.

The bone implants are configured for use in, for example, minimally invasive midline lumbar fusion, posterior cervical fusion, and oral maxillofacial revision surgery. Bone implants may also be used to heal vertebral compression fractures, interbody fusion, additional minimally invasive surgery, posterolateral fusion surgery, correction of adult or pediatric scoliosis, treatment of long bone defects, osteochondral defects, crest augmentation (dental/craniomaxillofacial, e.g., edentulous patients), trauma subplating, tibial plateau defects, filling bone cysts, wound healing, peritraumatic, plastic (cosmetic/plastic/reconstructive surgery), and other uses.

Covering 18 is biodegradable and is configured to be rolled into a generally tubular configuration having a diameter D for at least partially encapsulating bone material 12. It should be understood that the covering may also be made of a non-biodegradable material, or may be made of both a biodegradable material and a non-biodegradable material.

The cover 18 defines a generally planar surface 19 having a first edge 14, a second edge 16, a third edge 20, and a fourth edge 22. The first edge 14 is positioned opposite the second edge 16 and the third edge 20 is positioned opposite the fourth edge 22. In some aspects, the surface 19 is configured as a square or rectangle that can be rolled to a different or variable width W, a different or variable length L, or a different or variable diameter, as shown in fig. 4A, 4B, and 6. In this way, the implant can be customized to meet different sized bone defects.

First edge 14 includes at least one closure member 24 configured to maintain covering 18 in a coiled configuration having a predetermined diameter D for at least partially encapsulating bone material 12. In some aspects, the third and

fourth edges

20, 22 may be sealed by suture or adhesive or other comparable methods by the practicing clinician when used at the surgical site, for example.

In various embodiments, the cover 18 includes, consists essentially of, or consists of a mesh 32. The web 32 has an inner surface 34 and an outer surface 36, as shown in fig. 5A and 5B. As further described in this disclosure, both the length and width of the mesh may be adjusted by trimming the mesh to any desired size prior to winding the mesh to fully or partially encapsulate the bone material. Thus, the rolled mesh of the present application can be customized to match the anatomy of the patient as desired at the surgical site.

The inner or outer surface may include a plurality of spaced apart internal indicia 38 (not shown) or external indicia 40 configured to assist in sizing the cover 18 or mesh 32. The indicia 38 may be a web of lines of different colors, or other visual indicators, such as notches, knots, bumps, and the like. For example, in fig. 6, the indicia 40 comprise different colored lines extending longitudinally at different lengths along the length of the cover 18 to assist the surgeon or another clinician in resizing the mesh to form a desired rolled product of a particular diameter. Fluorescent surgical dyes and/or coloring additives approved for use with medical devices may be used. For example, useful dyes include, but are not limited to, D & C blue No. 6, D & C blue No. 9, D & C green No. 5, [ phthalocyanine (2-) ] copper, FD & C blue No. 2, chromium-cobalt-aluminum oxide, ferric ammonium citrate, pyrogallol, or hematoxylin extract.

In various embodiments, the cover 18 may have different lengths and widths. In some embodiments, the width of the cover 18 defines the circumference of the rolled cover and may vary from about 10mm to about 100mm, more particularly from about 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17mm, 18mm, 19mm, 20mm, 21mm, 22mm, 23mm, 24mm, 25mm, 26mm, 27mm, 28mm, 29mm, 30mm, 31mm, 32mm, 33mm, 34mm, 35mm, 36mm, 37mm, 38mm, 39mm, 40mm, 41mm, 42mm, 43mm, 44mm, 45mm, 46mm, 47mm, 48mm, 49mm, 50mm, 51mm, 52mm, 53mm, 54mm, 23mm, 28mm, 27mm, 28mm, 29mm, 30mm, 31mm, 32mm, 33mm, 34mm, 35mm, 36mm, 37mm, 38mm, 39mm, 40mm, 41mm, 42mm, 43mm, 44mm, 45mm, 46mm, 47mm, 48mm, 49mm, 50mm, 51mm, 52mm, 53mm, 54mm, 23mm, or 55mm, 56mm, 57mm, 58mm, 59mm, 60mm, 61mm, 62mm, 63mm, 64mm, 65mm, 66mm, 67mm, 68mm, 69mm, 70mm, 71mm, 72mm, 73mm, 74mm, 75mm, 76mm, 77mm, 78mm, 79mm, 80mm, 81mm, 82mm, 83mm, 84mm, 85mm, 86mm, 87mm, 88mm, 89mm, 90mm, 91mm, 92mm, 93mm, 94mm, 95mm, 96mm, 97mm, 98mm, 99mm to about 100mm. In some embodiments, the rolled cover may have a length ranging from about 2cm, 4cm, 6cm, 8cm, 10cm, 12cm, 14cm, 16cm, 18cm, 20cm, 22cm, and 24 cm. In one embodiment, the length of the rolled cover may vary from about 4cm to about 14cm.

The diameter of the wound cover may be from about 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17mm, 18mm, 19mm, 20mm, 21mm, 22mm, 23mm, 24mm, 25mm, 26mm, 27mm, 28mm, 29mm, 30mm, 31mm, 32mm, 33mm, 34mm, 35mm, 36mm, 37mm, 38mm, 39mm, 40mm, 41mm, 42mm, 43mm, 44mm, 45mm, 46mm, 47mm, 48mm, 49mm, 50mm 51mm, 52mm, 53mm, 54mm, 55mm, 56mm, 57mm, 58mm, 59mm, 60mm, 61mm, 62mm, 63mm, 64mm, 65mm, 66mm, 67mm, 68mm, 69mm, 70mm, 71mm, 72mm, 73mm, 74mm, 75mm, 76mm, 77mm, 78mm, 79mm, 80mm, 81mm, 82mm, 83mm, 84mm, 85mm, 86mm, 87mm, 88mm, 89mm, 90mm, 91mm, 92mm, 93mm, 94mm, 95mm, 96mm, 97mm, 98mm, 99mm to about 100mm. In one embodiment, the diameter of the rolled cover may vary from about 7mm to about 25mm.

In the embodiment shown in fig. 6, the markings 40 are provided at specific lengths along the length of the covering, such as at 22mm, 38mm, 53mm, 69mm, and 88mm, which may enable the surgeon to trim the covering at these dimensions.

As shown in fig. 4A, 4B, and 6, at least one closure member 24 may be positioned on the first edge 14 or the third edge 20 of the covering 18. In other embodiments, the closure member may be positioned on the second edge 16 and/or the fourth edge 22. Whether attached to or detached from the covering, the closing member functions to maintain the covering 18 in a coiled configuration for at least partially encapsulating the bone material 12. As also shown in fig. 4A, 4B, and 6, closure member 24 may comprise, consist essentially of, or consist of one or more strands 42 configured to be tied. The strands 42 may be disposed at various distances along the length or width of any of the edges of the cover 18.

In some embodiments, the strands are disposed on the edge of the cover 18 opposite the wrapping edge. For example, in one aspect, wrapping the covering about the second edge 16 would require at least one closure member 24 disposed about the first edge 14. In some embodiments , the strands 42 may be spaced apart at predefined intervals , at intervals of from about 0.5cm , 0.6cm , 0.7cm , 0.8cm , 0.9cm , 1.0cm , 1.2cm , 1.4cm , 1.5cm , 1.6cm , 1.7cm , 1.8cm , 1.9cm , 2.0cm , 2.2cm , 2.3cm , 2.4cm , 2.5cm , 2.6cm , 2.7cm , 2.8cm , 2.9cm , 3.0cm , 3.1cm , 3.2cm , 3.3cm , 3.4cm , 3.5cm , 3.6cm , 3.7cm , 3.8cm , 3.9cm , 4.0cm , 4.1cm , 4.2cm , 4.4cm , 4.5cm , 4.6cm , 4.7cm , 4.8cm , 4.9cm , 5.0cm , 5.1cm , 5.2cm , 5.2cm , 5.3cm , 5.5cm , 5.6cm , 5.7cm , 5.8cm , 5.9cm , 6.0cm , 6.1cm , 6.2cm , 6.3cm , 6.4cm , 6.5cm , 6.6cm , 6.7cm , 6.8cm , 6.9cm , 7cm , 7.1cm , 7.2cm , 7.3cm , 7.4cm , 7.5cm , 7.6cm , 7.7cm , 7.8cm , 7.9cm , 8cm , 8.1cm , 8.2cm , 8.3cm , 8.4cm , 8.5cm , 8.6cm , 8.7cm , 8.8cm , 8.9cm , 9cm , 9.1cm , 9.2cm , 9.3cm , 9.4cm , 9.5cm , 9.6cm , 9.7cm , 9.8cm , 9.9cm to about 10cm. . Thus, mesh 32 includes its own self-closing strands 42 that can secure bone material in a coiled mesh that can be customized to any desired width, length, and/or diameter combination. By providing an adjustable mesh with built-in self-closing and/or self-sealing features, bone material may be completely contained and will not migrate from the surgical site. In this manner, mesh 32 enables the clinician to provide a rolled mesh that can be filled with any type and any volume of any desired bone material.

In fig. 5A, the wound web 32 is shown with the V-shaped strands 42 in an untextured configuration. In fig. 5B, strands 42 are tied around the wound mesh 32. Similarly, fig. 1 shows closure member 24 tied around covering 18 to secure bone material within the wrapped covering.

The strands may be formed of the same material as the mesh or a different material from the mesh, and may be interwoven or integrated into the fabric of the mesh. The strands may be manufactured via coating, 3D printing and/or screen printing. In some embodiments, the strands are made of non-absorbable silk, nylon, cabled nylon, polyester, and polypropylene. In other embodiments, the strands are biodegradable and resorbable and may be made from polyglycolic acid (PGA), rapid polyglycolic acid (RPGA), polydioxanone (PDO), and polycarbophil or polyglycolide-caprolactone (PGCL). In some embodiments, the strands may be made of hydroxyapatite, calcium phosphate, ceramic, or a combination thereof.

In various embodiments, the strands may have a length ranging from about 5cm, 6cm, 7cm, 8cm, 9cm, 10cm, 11cm, 12cm, 13cm, 14cm, 15cm, 16cm, 17cm, 18cm, 19cm, 20cm, 21cm, 22cm, 23cm, 24cm, 25cm, 26cm, 27cm, 28cm, 29cm, 30cm, 31cm to about 32 cm. In many embodiments, the diameter of each strand may vary with its material. For example, in some aspects, for a non-absorbable strand, the diameter of each strand may vary from about 0.01mm, 0.02mm, 0.03mm, 0.04mm, 0.05mm, 0.06mm, 0.07mm, 0.08mm, 0.09mm, 0.1mm, 0.15mm, 0.2mm, 0.3mm, 0.35mm, 0.4mm, 0.5mm, 0.6mm, 0.7mm, 0.8mm to about 0.9mm. In some aspects, for resorbable strands, the diameter of each strand may vary from about 0.02mm, 0.03mm, 0.04mm, 0.05mm, 0.06mm, 0.07mm, 0.08mm, 0.09mm, 0.1mm, 0.15mm, 0.2mm, 0.3mm, 0.35mm, 0.4mm, 0.5mm, 0.6mm, 0.7mm, 0.8mm to about 0.9mm.

To assist the surgeon or clinician in resizing the covering at the surgical site, strands 42 are disposed on either of the edges of covering 18 and may also be of different colors to indicate the length of the dimension along the covering. The dyes that may be used for the strands of the cover may be the same kind of dyes that may be used to color other indicia or visual indicators present on the cover 18 as shown in fig. 6.

In various embodiments, the cover can have a number of configurations as shown in fig. 7A-7E. For example, in fig. 7A, the cover 18 has a planar or unrolled configuration; in fig. 7B, the cover 18 is in a rolled configuration; and in fig. 7C, the cover 18 is partially rolled. In fig. 7D and 7E, the cover 18 has a tubular configuration with different diameter sizes.

In some embodiments, when in the coiled configuration, covering 18 has opposing open ends 60 and 62 configured to be pulled in opposite directions along axisbase:Sub>A-base:Sub>A to reduce the diameter of the covering, thereby at least partially encapsulating bone material within the covering, as shown in fig. 7D. In these embodiments, the clinician can begin with rolling the covering intobase:Sub>A tubular shape withbase:Sub>A large diameter, loading it with bone graft, and then pulling along the long axisbase:Sub>A-base:Sub>A as shown in fig. 7D so that the covering can collapse around the enclosed bone graft.

In some embodiments, the tubular cover is configured to be adjusted to different diameters by using sizing rings 44 of different diameters (e.g., d1, d2, d3, etc., as shown in fig. 8A, 8B, and 8C). In other embodiments, as shown in fig. 9A, instead of pulling along the major axisbase:Sub>A-base:Sub>A to collapse the coiled covering around the bone material, the clinician can squeeze the bone material within the tubular covering tobase:Sub>A controlled diameter by using sizing cylinders 46 of different diameters. The ring and sizing cylinder may have a diameter of from about 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17mm, 18mm, 19mm, 20mm, 21mm, 22mm, 23mm, 24mm, 25mm, 26mm, 27mm, 28mm, 29mm, 30mm, 31mm, 32mm, 33mm, 34mm, 35mm, 36mm, 37mm, 38mm, 39mm, 40mm, 41mm, 42mm, 43mm, 44mm, 45mm, 46mm, 47mm, 48mm, 49mm, 50mm 51mm, 52mm, 53mm, 54mm, 55mm, 56mm, 57mm, 58mm, 59mm, 60mm, 61mm, 62mm, 63mm, 64mm, 65mm, 66mm, 67mm, 68mm, 69mm, 70mm, 71mm, 72mm, 73mm, 74mm, 75mm, 76mm, 77mm, 78mm, 79mm, 80mm, 81mm, 82mm, 83mm, 84mm, 85mm, 86mm, 87mm, 88mm, 89mm, 90mm, 91mm, 92mm, 93mm, 94mm, 95mm, 96mm, 97mm, 98mm, 99mm to a diameter of about 100 mm.

In other embodiments, as shown in fig. 9B, the clinician may start with a cover of small diameter but enlarge the diameter by adding excess bone material. In these embodiments, as shown in fig. 9B, funnels 48 of different diameters are used to load the covering with bone material. The funnel may have a size of from about 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17mm, 18mm, 19mm, 20mm, 21mm, 22mm, 23mm, 24mm, 25mm, 26mm, 27mm, 28mm, 29mm, 30mm, 31mm, 32mm, 33mm, 34mm, 35mm, 36mm, 37mm, 38mm, 39mm, 40mm, 41mm, 42mm, 43mm, 44mm, 45mm, 46mm, 47mm, 48mm, 49mm, 50mm, 51mm 52mm, 53mm, 54mm, 55mm, 56mm, 57mm, 58mm, 59mm, 60mm, 61mm, 62mm, 63mm, 64mm, 65mm, 66mm, 67mm, 68mm, 69mm, 70mm, 71mm, 72mm, 73mm, 74mm, 75mm, 76mm, 77mm, 78mm, 79mm, 80mm, 81mm, 82mm, 83mm, 84mm, 85mm, 86mm, 87mm, 88mm, 89mm, 90mm, 91mm, 92mm, 93mm, 94mm, 95mm, 96mm, 97mm, 98mm, 99mm to a diameter of about 100 mm. The clinician can achieve similar results by loading the rolled cover with a variable diameter funnel 50 as shown in fig. 10.

As shown in fig. 12, the cover 18 of the bone implant 10 can include a body portion 80 and a closure portion 82 adjacent the body portion. As in other embodiments described in this application, the covering shown in fig. 12 can be a biodegradable mesh. By controlling the spacing of the wires in the body portion and the closure portion, the porosity of the covering (e.g., mesh) can be controlled, and thus the inflow and outflow of cells and other materials that allow bone growth can be controlled.

By varying the pattern of the threads of the woven mesh, the mechanical properties of the covering can be varied. For example, the body portion 80 of the cover 18 can include, consist essentially of, or consist of a configuration similar to that of fishing net, with the netting twine 84 being woven in a narrower pattern (e.g., a generally rectangular pattern as shown in fig. 12). The lines are narrowly spaced from each other. In the narrower pattern of the body portion 80, the threads 84 are woven more tightly to produce a mesh with less porosity. In some embodiments, the pore size of the body portion can be, for example, from about 100 μm to about 200 μm.

The closure portion 82 may include, consist essentially of, or consist of mesh strands 86 woven in a wider pattern (e.g., a generally diamond shape as shown in fig. 12). The lines are spaced apart more than the body portion. The threads 86 of the closure portion 82 are woven more loosely to create a mesh with greater porosity. In some embodiments, the pore size may be, for example, about 0.1mm to about 2mm. In some embodiments, the aperture size of the closure portion 82 varies from about 0.1mm to about 5mm, about 0.5mm to about 3mm, or about 1mm to about 2mm. The closure portion will be more resilient and when the covering is wrapped, the closure portion can be wrapped around the body portion with the narrower woven threads, and then the body portion can be positioned within the separate wider threads of the closure portion to at least partially encapsulate the bone material within the covering.

In some embodiments, a covering having threads woven in different geometric patterns to achieve different mechanical properties at different locations on the covering may be provided by 3D printing. Three-dimensional (3D) printing is an additive printing process for manufacturing three-dimensional solid objects from digital models. 3D printing techniques are considered additive processes because they involve the application of successive layers of material to produce a printed object. Conventional 3D printing allows objects to be created by depositing material one layer at a time on a flat fabrication platform. Once the first layer is deposited, a second layer is deposited on top of the first layer. This process is repeated as necessary to produce a multi-layered solid object. More recently, computer-implemented devices and methods for producing a covering (e.g., a mesh) for a bone implant have become available as described in US 10064726 and US 10442175, assigned to warraw Orthopedic, incorporated by reference as if fully set forth herein. Thus, conventional weaving, knitting, injection molding, or computer-implemented 3D printing methods may be used to create a covering 18 having one geometry for the lines of the body portion and a different geometry for the lines of the closure portion, however, in both cases, a covering with a continuous surface is created.

In various embodiments, the body portion 80 and the closure portion 82 are disposed adjacent to one another as a continuous covering or web having location-specific mechanical properties. In some aspects, the body portion 80 includes a mesh woven from inelastic, non-stretchable threads 88, which may be porous or non-porous, as shown in fig. 13A. The closure portion 82 is more flexible, including a mesh made of inelastic, non-stretchable threads 90 printed in a sinusoidal pattern to impart structural elasticity (stretchability) to the closure portion 82, and may be wrapped around the body portion to hold the covering in a wrapped configuration to a predetermined diameter to at least partially encapsulate the bone material, as shown in fig. 13B. In some embodiments, the closure portion 82 includes multiple high porosity layers that may be wrapped around the body portion 80. In some embodiments, the closure portion 82 may be stretched and wrapped around the body portion 80 without adding any substantial amount of additional polymer mesh or without significantly reducing the body porosity. In some embodiments, the closure portion is (i) more flexible than the body portion or (ii) more deformable than the body portion.

In some embodiments, the bone material may comprise hydroxyapatite, calcium phosphate, and/or a ceramic (e.g., 90-95% hydroxyapatite). Bone material (e.g., hydroxyapatite, calcium phosphate, and/or ceramic) may be made into one or more threads or yarns of a covering (e.g., mesh). In some embodiments, a bone material (e.g., hydroxyapatite, calcium phosphate, and/or ceramic) may be combined with a polymer and form one or more threads or yarns of the covering. For example, the threads or yarns of the covering can be made of a superelastic bone material. This may be part of the body portion and/or the closure portion of the cover.

In some embodiments, the cover 18 is prepared by 3D printing, and in some aspects, the ink used in the printing process may be inherently tacky. Once wound, the resulting covering may remain partially or fully wound due to the tackiness of its material, as shown in fig. 7B and 7C. In other embodiments, suitable materials include natural materials, synthetic polymeric resorbable materials, synthetic polymeric non-resorbable materials, and other materials. Natural mesh materials include silk, extracellular matrix (such as DBM, collagen, ligament, tendon tissue, or others), silk-elastin, collagen, and cellulose. Synthetic polymeric resorbable materials include poly (lactic acid) (PLA), poly (glycolic acid) (PGA), poly (lactic-glycolic acid) (PLGA), polydioxanone, PVA, polyurethane, polycarbonate, and the like.

In some embodiments, the body portion 80 may be prepared from a first set of threads 84 and the closure portion 82 may be prepared from a second set of threads 86. The

wires

84 and 86 may be made of the same or different materials. However, in some aspects, the threads of the cover may be woven differently to achieve different mechanical properties. In some embodiments, a print head of a 3D printing device may be configured to extrude more than one type of material for printing the covering 18. In other embodiments, the 3D printing device may have a first printhead configured to extrude a first material to form the line 84 and a second printhead configured to extrude a second material to form the line 86. Suitable materials for making the cover 18 include natural materials, synthetic polymeric resorbable materials, synthetic polymeric non-resorbable materials, and other materials. Natural mesh materials include silk, extracellular matrix (such as DBM, collagen, ligament, tendon tissue, or others), silk-elastin, collagen, and cellulose. Synthetic polymeric resorbable materials include poly (lactic acid) (PLA), poly (glycolic acid) (PGA), poly (lactic-co-glycolic acid) (PLGA), polydioxanone, PVA, polyurethane, polycarbonate, and the like.

In some embodiments, whether 3D printed or not, the covering 18 or mesh 32 can be made of a shape memory polymer and/or alloy to allow the mesh to move from a planar configuration to a coiled configuration to at least partially encapsulate the bone material without the need for a locking or tying mechanism, as shown in fig. 7B and 7C. In other embodiments, the web may be designed to include hooks to adhere to specific portions of the web. For example, in some aspects, 3D printed hooks can be deposited by layering by printing flowable inks onto the printed surface of the web, wherein particular portions contain voids into which the inks can flow and cure. Upon removal of the 3D printed mesh from the printed surface, the mesh retains positive protrusions that match the voids. These protrusions act like hooks and can interact with the web to allow the web to adhere to itself in a rolled configuration. In one embodiment, the first mating surface of the web comprises protrusions or hooks (31 of fig. 14A) and the second mating surface comprises mating voids (35 of fig. 14B) for holding the web in a rolled configuration. In another embodiment, referring to fig. 4B, cover 18 may have hooks or other protrusions (not shown) on first edge 14 as an alternative to strands 42. The opposite second edge 16 may have a matching void (not shown) for holding the mesh in a rolled configuration.

Fig. 14A is a schematic view of a flat covering for securing bone material, as in other embodiments of the coverings described in the present disclosure, with the interior of the covering (e.g., mesh) having a plurality of spaced apart visual indicia 40 to aid in resizing the covering. The markings 40 are positioned at predefined intervals to assist the user in resizing the covering to form a rolled covering of a particular diameter. The indicia 40 may be lines of different colors, or other visual indicators, such as notches, knots, protrusions, and the like. The different colored threads may extend longitudinally or transversely and may be used to indicate different sizes to assist the surgeon in resizing the mesh to produce a particular diameter, length and width of the rolled mesh.

As otherwise shown, the web 32 includes an inner portion 34 (shown in FIG. 14A) and an outer portion 36 (shown in FIG. 14B). In some aspects, all or a portion of the interior and/or exterior of the web includes an adhesive material disposed thereon. In other embodiments, the mesh comprises an inner portion and an outer portion, a portion of the inner and/or outer portion having a mating surface configured to hold the mesh in a rolled configuration.

In some embodiments, the web may be held in a rolled configuration by the use of an adhesive. In the embodiment of fig. 14A, the web 32 has an adhesive 92, shown as a strip, on the right side of the interior 34 of the flat covering that is configured to be attached to the outer surface 36 (shown in fig. 14B) of the web 32 after it is rolled as shown in fig. 14B. The adhesive 92 may have a release layer 93 that may be removed before, during, or after winding to expose the adhesive.

In some embodiments, the adhesive may be at discrete areas of the covering or on the entire interior and/or exterior of the covering. In some embodiments, the adhesive may be added to the cover before, during, or after the cover is wound to the desired diameter, length, and/or width.

In various embodiments, the binder material is (i) water activated; (ii) the adhesive material is applied at the time of use; (iii) The binder material contains a volatile solvent which, upon evaporation, renders the web tacky to provide self-adhesion. When the adhesive material is applied at the time of use, the adhesive may be provided in a separate container (e.g., a bottle) and applied, for example, by adding a glue string after the mesh is wound to encapsulate the bone material.

In various embodiments, suitable adhesive materials for closing the mesh into a rolled or partially rolled configuration may include, for example, cyanoacrylate (such as tissue adhesive (histoacryl) by B Braun which is n-butyl-2 cyanoacrylate; or Dermasbond which is 2-octyl cyanoacrylate); epoxy-based compounds, dental resin sealants, dental resin cements, glass ionomer cements, polymethylmethacrylate, gelatin-resorcinol-formaldehyde glue, collagen-based glue, inorganic binders such as zinc phosphate, magnesium phosphate or other phosphate-based binders, zinc carboxylates, L-DOPA (3, 4-dihydroxy-L-phenylalanine), proteins, carbohydrates, glycoproteins, mucopolysaccharides, other polysaccharides, hydrogels, protein-based binders such as fibrin glue and mussel-derived adhesive protein, and any other suitable substance. The adhesives may be selected for use based on their bonding time; for example, in some cases, temporary adhesives may be required, e.g., for fixation during and after a surgical procedure for a limited time, while in other cases permanent adhesives may be required. In some embodiments, the bone implant may be sealed by applying a volatile or water-soluble solvent to the mesh material, which temporarily softens the mesh or causes the surface of the mesh to dissolve, which enables the mesh to bind and adhere to an adjacent mesh. Once the volatile or water-soluble solvent is removed from the application site, the web will harden or precipitate, thereby forming a bond between the two portions of the web at the site of application of the solvent. In the case where the web is made of a resorbable material, an adhesive may be chosen that remains adherent when the material is present in the body.

Net

In various embodiments, the cover 18 is an adjustable, biodegradable mesh. The mesh may be made of woven threads configured to allow cellular ingrowth while also retaining bone material within the compartment of the bone implant. The strands of the mesh may have a predetermined thickness of about 0.01mm to about 2.0mm, about 0.05mm to about 1.0mm, or about 0.1mm to about 0.5 mm. The thickness of the lines may be uniform along the length of each line or vary across the length of each line. In some embodiments, some of the wires have a greater thickness than other wires. The lines may be sized to allow for customizable apertures between the lines. In some embodiments, the bone implant is configured to facilitate the transfer of substances and/or materials around the surgical site. After implantation at the surgical site, the bone implant may participate, control, or otherwise adjust, or may allow penetration of the mesh by surrounding materials, such as cells or tissue.

The web is configured to be wound to a diameter as shown in fig. 1, 2, 3, 5A, 5B, 7D, 7E, and 14B. The mesh is a fully customizable mesh that can be adjusted in both length and diameter to resize according to the needs of a particular patient's anatomy. For example, the mesh may include a diameter dimension of between about 1mm to about 100mm in diameter. In some embodiments, the mesh comprises a diameter of about 2mm, 5mm, 10mm, 15mm, 20mm, 25mm, 30mm, 35mm, 40mm, 45mm, 50mm, 55mm, 60mm, 65mm, 70mm, 75mm, 80mm, 85mm, 90mm, 95mm, or 100 mm. In some embodiments, the mesh comprises a length or width between about 0.1cm to about 24 cm. In some embodiments, the web comprises a length or width of about 0.1cm, 0.2cm, 0.3cm, 0.35cm, 0.4cm, 0.5cm, 0.6cm, 0.7cm, 0.8cm, 0.9cm, 1cm, 2cm, 3cm, 4cm, 5cm, 6cm, 7cm, 8cm, 9cm, 10cm, 11cm, 12cm, 13cm, 14cm, 15cm, 16cm, 17cm, 18cm, 19cm, 20cm, 21cm, 22cm, 23cm, or 24 cm.

The mesh may be a porous mesh such that fluid transfer and cellular infiltration may occur such that osteoblasts may fabricate a bone graft. For example, in fig. 6, the mesh 32 shows the holes at 33A and 33B as an exploded view. In many embodiments, when the bone material is completely encapsulated by the mesh, the mesh is porous to allow cellular influx and efflux. To optimize cell or fluid migration through the mesh, the pore size may be optimized for the viscosity and surface tension of the fluid or the size of the cells. The porous web may have a pore size of about 1 micron to about 2000 microns, about 1 micron to about 1500 microns, about 1 micron to about 1000 microns, about 1 micron to about 500 microns, about 1 micron to about 250 microns, about 100 microns to about 2000 microns, about 150 microns to about 1500 microns, about 200 microns to about 1000 microns, about 250 microns to about 500 microns. In some embodiments, the pore size may be about 1 micron, 10 microns, 20 microns, 50 microns, 80 microns, 100 microns, 120 microns, 150 microns, 180 microns, 200 microns, 220 microns, 250 microns, 280 microns, 300 microns, 350 microns, 400 microns, 450 microns, 500 microns, 550 microns, 600 microns, 650 microns, 700 microns, 750 microns, 800 microns, 850 microns, 900 microns, 950 microns, 1000 microns, 1250 microns, 1450 microns, 1650 microns, 1850 microns, 2000 microns, 2100 microns, 2200 microns, 2300 microns, 2400 microns, 2500 microns, or 2600 microns. Generally, the mesh should have a pore size small enough to hold bone material from falling through the mesh.

The web may have varying degrees of permeability at its surface. It may be permeable, semi-permeable or impermeable. The permeability may be associated with cells, fluids, proteins, growth factors, bone morphogenic proteins, or others. In other embodiments, the material may be woven.

The web may have any suitable customized configuration. In various configurations, the mesh can be customized into tubular configurations of various diameters and lengths that can be easily fitted into the patient's anatomy.

Further, in some embodiments, the flexible nature of the rolled web allows the web to be manipulated into multiple compartments. For example, in a tubular embodiment, the tube may be formed into multiple compartments by tying the strands at one or more points around the tube, or by other suitable mechanisms such as crimping, twisting, knotting, stapling, or suturing.

In some embodiments, the mesh may be labeled. Such tagging may be performed in any suitable manner and at any suitable location on the web. In some embodiments, labeling may be performed by using screen printing, using a modified weave or knot pattern, by using different colored threads, or other means. The superscript may indicate information about the net. Such information may include part numbers, donor ID numbers, numbers indicating the order of use or implant size in the procedure, letters or words, and the like. In some embodiments, the mesh may be color specific to help provide the correct orientation of the mesh before or during filling and to confirm that the plurality of protrusions and/or plurality of depressions of the mesh are oriented to optimize their engagement. In some embodiments, a portion of the mesh or the entire mesh is colored blue, purple, pink, orange, yellow, green, or red.

The mesh may be closed after it is wound to at least partially or completely encapsulate the bone material. Thus, the bone implant may be provided in an unfilled, non-sealed state. After the substance to be delivered is placed in the coiled bone implant, the mesh of the bone implant may be permanently or temporarily closed by one or more strands configured to be tied or otherwise secured. In addition, temporary closure may also be achieved by fold locking, tightening, adhesive, or other means. The temporarily closed bone implant may be opened during surgical implantation without damaging the mesh to add or remove substances in the bone implant.

In some embodiments, the coiled mesh may completely encapsulate the bone material, wherein the coiled mesh surrounds the entire bone material (e.g., bone particles, bone cement, etc.) to completely encapsulate the bone material, as shown in fig. 7B. In some embodiments, the mesh may be partially wrapped around and partially encapsulate the bone material (e.g., bone particles, bone cement, etc.), wherein the mesh surrounds a portion of the bone material, leaving a portion of the bone material unencapsulated by the mesh, as shown in fig. 7C.

The bone material of the bone implant may include fully demineralized bone fibers and surface demineralized bone fragments. Bone material also includes fibers, powders, chips, triangular prisms, spheres, cubes, cylinders, chips, or other shapes having irregular or random geometries. These may comprise, for example, "substantially demineralized," "partially demineralized," or "fully demineralized" cortical and/or cancellous bone. These also contain surface demineralizing substances, wherein the surfaces of the bone constructs are substantially demineralized, partially demineralized, or fully demineralized, while the bulk of the bone constructs are fully mineralized.

In some embodiments, the bone implant is configured to be self-sealing or sealed via chemical fusion, thermal treatment, self-fusing material, self-adhering material, adhesive, or a combination thereof, and to encapsulate bone material. In some embodiments, adhesives that may be used include, but are not limited to, cyanoacrylates (tissue adhesives such as B Braun, which is n-butyl-2 cyanoacrylate; or dermobond, which is 2-octyl cyanoacrylate), epoxy compounds, dental resin sealants, dental resin cements, glass ionomer cements, polymethylmethacrylate, gelatin-resorcinol-formaldehyde glue, collagen-based glues, inorganic binders such as zinc phosphate, magnesium phosphate, or other phosphate-based binders, zinc carboxylates, L-DOPA (3, 4-dihydroxy-L-phenylalanine), proteins, carbohydrates, glycoproteins, mucopolysaccharides, other polysaccharides, hydrogels, protein-based binders such as fibrin glue and mussel-derived adhesive protein, and any other suitable substance. In some embodiments, the bone implant may be sealed by mechanical means such as, for example, zippers, sutures, staples, pins, snaps, clips, or combinations thereof. In some embodiments, the bone implant may be sealed by applying a volatile or water-soluble solvent to the mesh material, which temporarily softens the mesh or causes the surface of the mesh to dissolve, which enables the mesh to bind and adhere to an adjacent mesh. Once the volatile or water-soluble solvent is removed from the application site, the web will harden or precipitate, forming a bond between the two portions of the web at the application site of the solvent.

In some embodiments, the wound web may be left closed or sealed for about 1 hour to about 2 hours. When used with wet or dry bone material, the temporary or permanent closure or sealing of the mesh should be compatible and still function.

In some embodiments, the bone implant is configured to be self-sealing or sealed via chemical fusion, thermal treatment, self-fusing material, self-adhering material, adhesive, or a combination thereof, and to encapsulate bone material. In some embodiments, adhesives that may be used include, but are not limited to, cyanoacrylates (tissue adhesives such as B Braun, which is n-butyl-2 cyanoacrylate; or dermobond, which is 2-octyl cyanoacrylate), epoxy compounds, dental resin sealants, dental resin cements, glass ionomer cements, polymethylmethacrylate, gelatin-resorcinol-formaldehyde glue, collagen-based glues, inorganic binders such as zinc phosphate, magnesium phosphate, or other phosphate-based binders, zinc carboxylates, L-DOPA (3, 4-dihydroxy-L-phenylalanine), proteins, carbohydrates, glycoproteins, mucopolysaccharides, other polysaccharides, hydrogels, protein-based binders such as fibrin glue and mussel-derived adhesive protein, and any other suitable substance. In some embodiments, the bone implant may be sealed by mechanical means such as, for example, zippers, sutures, staples, pins, snaps, clips, or combinations thereof.

In some embodiments, the biological attachment may be by a mechanism that promotes tissue ingrowth, such as by a porous coating or a hydroxyapatite-tricalcium phosphate (HA/TCP) coating. Generally, hydroxyapatite is bound by the biological action of new tissue formation. A porous ingrowth surface such as titanium alloy material or tantalum porous metal or trabecular metal in a bead coating may be used and adhesion is promoted at least by promoting bone growth through the porous implant surface. These mechanisms may be referred to as bioadhesion mechanisms. In some embodiments, the bone implant may be attached to the tissue structure by a wrap, suture, wire, strip, elastic band, cable or cable tie, or a combination thereof or another fastener.

In other embodiments, suitable substances for forming the mesh of the bone implant include natural materials, synthetic polymeric resorbable materials, synthetic polymeric non-resorbable materials, and other materials. Natural mesh materials include silk, extracellular matrix (such as DBM, collagen, ligament, tendon tissue, or others), silk-elastin, collagen, and cellulose. Synthetic polymeric resorbable materials include poly (lactic acid) (PLA), poly (glycolic acid) (PGA), poly (lactic-co-glycolic acid) (PLGA), polydioxanone, PVA, polyurethane, polycarbonate, and the like. In some embodiments, the mesh may be made of hydroxyapatite, calcium phosphate, ceramic, or a combination thereof.

In some embodiments, the mesh may be made of a memory shape polymer and/or alloy to allow the mesh to move from a planar configuration to a coiled configuration to at least partially encapsulate the bone material without the need for a locking mechanism or a tying mechanism. Memory shape polymers include, but are not limited to, polyethers, polyacrylates, polyamides, polysiloxanes, polyurethanes, polyetheramides, polyurethane/ureas, polyetheresters, polynorbornenes, crosslinked polymers such as crosslinked polyethylene and crosslinked poly (cyclooctene), inorganic-organic hybrid polymers, and copolymers such as urethane/butadiene copolymers, styrene-butadiene copolymers.

The mesh may be absorbable and/or resorbable and is made of a material including, but not limited to, at least one material of poly (lactic acid) (PLA), poly (glycolic acid) (PGA), poly (lactic-co-glycolic acid) (PLGA), polydioxanone (PDO), allocollagen, xenocollagen, hydroxyapatite, calcium phosphate, ceramic, or a combination thereof. When formed of an absorbable or resorbable material, the mesh may be substantially resorbed within 2 weeks, within 3 weeks, within 4 weeks, within 12 weeks, within 16 weeks, within 20 weeks, within 24 weeks, within 28 weeks, within 32 weeks, within 36 weeks, within 40 weeks, within 44 weeks, within 48 weeks, within 52 weeks, or any other suitable time range. In some embodiments, the web may retain its strength over this period of time. In some embodiments, the mesh is expected to be resorbed about 6 months after implantation. In various embodiments, the mesh is biocompatible, meaning that the mesh is not expected to cause irritation or inflammation of surrounding tissue. To ensure biocompatibility and proper resorption, the pH of the surrounding tissue should be greater than about 3. Generally, the shelf life of webs that can be used with the implants described in this disclosure is expected to vary from about 2 years to 4 years. In some embodiments, the mesh may remain closed to at least partially encapsulate the bone material for at least 1 to 2 hours.

In some embodiments, the web itself may be tacky, such as where an adhesive is applied to the web or portions of the web so that the web may be maintained in a rolled configuration. The adhesive may be, for example, a bioadhesive, a glue, a cement, a cyanoacrylate, a silicone, a hot melt adhesive and/or a cellulosic bonding agent.

The material and configuration of the web may be selected or adjusted based on the desired release characteristics. Specific properties of the adjustable mesh include thickness, permeability, porosity, strength, flexibility, and/or elasticity. In some embodiments, the thickness and porosity of the mesh may contribute to its strength, flexibility, and elasticity. In some embodiments, the mesh may be made of a wet soft, moldable, tacky and/or tacky material to facilitate placement and packing of the bone implant to the surgical site.

The average molecular weight of the polymer used to make the web can be from about 1,000g/mol to about 10,000,000g/mol; or from about 1,000g/mol to about 1,000,000g/mol; or from about 5,000g/mol to about 500,000g/mol; or from about 10,000g/mol to about 100,000g/mol; or from about 20,000g/mol to about 50,000g/mol. In some embodiments of the present invention, the substrate is, the polymer has a molecular weight of 1,000 daltons, 2,000 daltons, 3,000 daltons, 4,000 daltons, 5,000 daltons, 6,000 daltons, 7,000 daltons, 8,000 daltons, 9,000 daltons, 10,000 daltons, 15,000 daltons, 20,000 daltons, 25,000 daltons, 30,000 daltons, 35,000 daltons, 40,000 daltons, 45,000 daltons, 50,000 daltons, 55,000 daltons, 60,000 daltons, 65,000 daltons, 70,000 daltons, 75,000 daltons, 80,000 daltons, 85,000 daltons, 90,000 daltons, 95,000 daltons, 100,000 daltons, 125,000 daltons, 150,000 daltons, 200,175,000 daltons, 225,000 daltons, 2,000 daltons, 3,000 daltons, 4,000 daltons, 5,000 daltons, 6,000 daltons, 5,000 daltons, and 250,000 daltons, 275,000 daltons, 300,000 daltons, 325,000 daltons, 350,000 daltons, 375,000 daltons, 400,000 daltons, 425,000 daltons, 450,000 daltons, 475,000 daltons, 500,000 daltons, 525,000 daltons, 550,000 daltons, 575,000 daltons, 600,000 daltons, 625,000 daltons, 650,000 daltons, 675,000 daltons, 700,000 daltons, 725,000 daltons, 750,000 daltons, 775,000 daltons, 800,000 daltons, 825,000 daltons, 850,000 daltons, 875,000 daltons, 900,000 daltons, 925,000 daltons, 950,000 daltons, 975,000 daltons, and/or 1,000,000 daltons.

The web may have varying degrees of permeability. It may be permeable, semi-permeable or impermeable. The permeability may be with respect to cells, fluids, proteins, growth factors, bone morphogenic proteins, or other substances. The web may be 1% to about 30% permeable, about 30% to about 70% permeable, or about 70% to about 95% permeable. The web may be 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% permeable.

In various embodiments, the mesh may encapsulate or partially encapsulate a bone material (e.g., DBM). In some embodiments, the mesh comprises a polymeric matrix that may have DBM fibers and/or DBM powders in its threads suspended in the polymeric matrix to promote cell transfer into and out of the mesh bag to induce bone growth at the surgical site. In other embodiments, the mesh further comprises mineralized bone fibers suspended in the polymer matrix. In some embodiments, the DBM powder is suspended in a polymer matrix between the DBM fibers and the mineralized bone fibers. In some embodiments, the DBM powder is suspended between the DBM fibers in the polymer matrix to reduce and/or eliminate the gaps that exist between the fibers. In some embodiments, the DBM powder is suspended between DBM fibers in a polymer matrix to improve osteoinductivity that promotes bone fusion (e.g., interspinous fusion).

In some embodiments, the polymer matrix comprises a bioerodible, bioabsorbable, and/or biodegradable biopolymer that can provide immediate release or sustained release. Examples of suitable sustained release biopolymers include, but are not limited to, poly (alpha-hydroxy acids), poly (lactide-co-glycolide) (PLGA), polylactides (PLA), polyglycolides (PG), polyethylene glycols (PEG), conjugates of poly (alpha-hydroxy acids), polyorthoesters (POE), polyaspirins, polyphosphazenes, collagen, starch, pregelatinized starch, hyaluronic acid, chitosan, gelatin, alginates, albumin, fibrin, vitamin E compounds (such as alpha-tocopheryl acetate, D-alpha-tocopheryl succinate), D, L-lactide or L-lactide, caprolactone, dextran, vinylpyrrolidone, polyvinyl alcohol (PVA), PVA-g-PLGA, PEGT-PBT copolymer (bioactive), PEO-PPO-PAA copolymer, PLGA-PEO-PLGA, PEG-PLGA, PLA-PLGA, poloxamer 407, PEG-PLGA-PEG triblock copolymer, SAIB (sucrose acetate isobutyrate), or combinations thereof. mPEG and/or PEG may be used as plasticizers for PLGA, but other polymers/excipients may be used to achieve the same effect. mPEG imparts ductility to the polymer.

In some embodiments, these biopolymers may also be coated on the mesh to provide the desired release profile or tissue ingrowth. In some embodiments, the coating thickness may be thin, for example, about 5 microns, 10 microns, 15 microns, 20 microns, 25 microns, 30 microns, 35 microns, 40 microns, 45 microns, or 50 microns to a thicker coating 60 microns, 65 microns, 70 microns, 75 microns, 80 microns, 85 microns, 90 microns, 95 microns, 100 microns to delay release of the substance from the bone implant. In some embodiments, the coating on the mesh ranges from about 5 microns to about 250 microns or from about 5 microns to about 200 microns. In some embodiments, the mesh comprises a polymeric coating, and the coating comprises a bioactive agent or bioactive material.

Any fully absorbable or resorbable material may be used to make the mesh, such as, for example, an absorbable polymer, such as poly (lactic acid) (PLA), poly (glycolic acid) (PGA), poly (lactic-co-glycolic acid) (PLGA), polydioxanone (PDO), allocollagen, xenocollagen, ceramic, hydroxyapatite, calcium phosphate, or a combination thereof. The mesh may be made of monofilament or multifilament threads or yarns, and the mesh may be manufactured using knitting, weaving, or the mesh may be non-woven, such as felted or point bonded, or manufactured using additive manufacturing methods (e.g., 3D printing). U.S. patents 10,064,726 and 10,442,175, which are incorporated by reference as if set forth in their entirety, describe 3D printing techniques that can be used to manufacture mesh implants for bone delivery described in this application. The mesh has a sufficiently large pore size so as not to impede cell transport and new bone formation. However, the pore size is small enough to adequately contain the graft material at the implantation site. Bone implants may be of various shapes and provided with instruments designed to facilitate intraoperative use and assembly. The bone implant enables streamlined assembly. Customization of the bone implant diameter and width enables the bone implant to be used in a variety of bone fusion repair procedures using smaller graft sizes, such as minimally invasive midline lumbar fusion, posterior cervical fusion, and oromaxillofacial repair procedures.

In some embodiments, the individual components of the mesh comprise poly (lactide-co-glycolide) (PLGA), polylactide (PLA), polyglycolide (PGA), D-lactide, D, L-lactide, D, L-lactide-co-epsilon-caprolactone, D, L-lactide-co-glycolide-co-epsilon-caprolactone, L-lactide-co-epsilon-caprolactone, hydroxyapatite, calcium phosphate, ceramic, or a combination thereof.

In some embodiments, the mesh further comprises a Bone Morphogenic Protein (BMP), a growth factor, an antibiotic, an angiogenesis-promoting material, a bioactive agent, or other active release material.

The mesh may be used to deliver a substance comprising any suitable biocompatible material. In particular embodiments, the mesh may be used to deliver surface demineralized bone fragments, optionally having a predetermined particle size, fully demineralized bone fibers, optionally compressed, and/or allografts. For embodiments where the substance is a biological substance, the substance may be autologous, allogeneic, xenogeneic or transgenic. Other suitable materials that may be placed in the mesh include, for example, proteins, nucleic acids, carbohydrates, lipids, collagen, allograft bone, autograft bone, cartilage stimulating substances, allograft cartilage, TCP, hydroxyapatite, calcium sulfate, polymers, nanofiber polymers, growth factors, growth factor carriers, tissue growth factor extracts, DBM, dentin, bone marrow aspirate in combination with various osteoinductive or osteoconductive carriers, lipid-derived or bone marrow-derived adult stem cell concentrates, umbilical cord-derived stem cells, adult or embryonic stem cells in combination with various osteoinductive or osteoconductive carriers, transfected cell lines, bone forming cells derived from periosteal, a combination of bone stimulating and cartilage stimulating materials, committed or partially committed cells from osteoblast or chondrocyte lineages, or a combination of any of the above.

According to some embodiments, the material to be placed in the hollow region of the coiled mesh may be supplemented, further treated, or chemically modified with one or more bioactive agents or bioactive compounds. As used herein, a bioactive agent or bioactive compound refers to a compound or entity that alters, inhibits, activates, or otherwise affects a biological or chemical event. For example, bioactive agents may include, but are not limited to: osteogenic or chondrogenic proteins or peptides; a DBM powder; collagen, insoluble collagen derivatives, and the like, as well as soluble solids and/or liquids dissolved therein; anti-AIDS substances; an anti-cancer substance; antimicrobial agents and/or antibiotics, such as erythromycin, bacitracin, neomycin, penicillin, polymyxin B, tetracycline, biotin, chloramphenicol, and streptomycin, cefazolin, ampicillin, aztreonam (azactam), tobramycin, clindamycin, gentamicin, and the like; an immunosuppressant; antiviral substances such as substances effective on hepatitis; an enzyme inhibitor; a hormone; a neurotoxin; (ii) an opioid; hypnotic drugs; an antihistamine; a lubricant; a sedative; an anticonvulsant; muscle relaxants and anti-parkinson agents; antispasmodics and muscle contractants, including channel blockers; miotics and anticholinergics; anti-glaucoma compounds; anti-parasitic and/or anti-protozoal compounds; a modulator of cell-extracellular matrix interaction comprising a cytostatic agent and an anti-adhesion molecule; a vasodilator; inhibitors of DNA, RNA or protein synthesis; anti-hypertensive agents; an analgesic agent; antipyretic medicine; steroidal and non-steroidal anti-inflammatory agents; anti-angiogenic factors; angiogenic factors and polymeric carriers containing such factors; anti-secretory factors; anticoagulants and/or antithrombotic agents; a local anesthetic; ophthalmic drugs; prostaglandins; an antidepressant; an antipsychotic agent; antiemetic agents; an imaging agent; biocidal/biostatic sugars such as dextran, glucose, and the like; an amino acid; a peptide; vitamins; an inorganic element; cofactors of protein synthesis; endocrine tissue or tissue fragments; a composition; enzymes such as alkaline phosphatase, collagenase, peptidase, oxidase, and the like; a polymer cell scaffold having parenchymal cells; a collagen lattice; an antigenic agent; a cytoskeletal agent; cartilage fragments; living cells such as chondrocytes, bone marrow cells, mesenchymal stem cells; a natural extract; genetically engineered or otherwise modified living cells; expanded or cultured cells; DNA delivered by a plasmid, viral vector, or other member; a tissue graft; autologous tissues such as blood, serum, soft tissue, bone marrow, etc.; a bioadhesive; bone morphogenic proteins (BMPs, including BMP-2); osteoinductive factor (IFO); fibronectin (FN); endothelial Cell Growth Factor (ECGF); vascular Endothelial Growth Factor (VEGF); cementum Attachment Extract (CAE); ketanserin; human Growth Hormone (HGH); an animal growth hormone; epidermal Growth Factor (EGF); interleukins, such as interleukin-1 (IL-1), interleukin-2 (IL-2); human alpha-thrombin; transforming growth factor (TGF-. Beta.); insulin-like growth factors (IGF-1, IGF-2); parathyroid hormone (PTH); platelet Derived Growth Factor (PDGF); fibroblast growth factor (FGF, BFGF, etc.); periodontal ligament chemotactic factor (PDLGF); enamel matrix proteins; growth and Differentiation Factor (GDF); the hedgehog family of proteins; a protein receptor molecule; small peptides derived from the above growth factors; a bone-promoting agent; a cytokine; somatotropin; a bone-eliminating compound; an anti-neoplastic agent; cell attractants and attachments; an immunosuppressant; penetration enhancers, for example fatty acid esters such as laurates, myristates and stearates of polyethylene glycol, enamine derivatives, alpha-ketoaldehydes; and a nucleic acid.

In certain embodiments, the bioactive agent may be a drug. In some embodiments, the bioactive agent may be a growth factor, cytokine, extracellular matrix molecule, or fragment or derivative thereof, e.g., a protein or peptide sequence, such as RGD.

In various embodiments, the mesh material of the bone implant may have an elastic modulus. As shown in fig. 13A, in some aspects, the body portion 80 of the covering 18 (or web 32) may be made of inelastic threads, while the closure portions 82 may be made of inelastic or elastic threads to ensure consistent wrapping around the body portion 80. In some embodiments, the closure portion 82 may have a thickness of about 1 × 10²To about 6X 10⁵Dyne/cm²Or 2X 10⁴To about 5X 10⁵Dyne/cm²Or 5X 10⁴To about 5X 10⁵Dyne/cm²The modulus of elasticity of (a). In some embodiments, the closure portion will be more resilient and when the covering is rolled, the closure portion can be wrapped around the body portion with the narrower woven threads, and then the body portion can be positioned within the separate wider threads of the closure portion to at least partially encapsulate the bone material within the covering in the rolled configuration.

The material may have functional properties. Alternatively, other materials having functional properties may be incorporated into the web. Functional properties may include radiopacity, antimicrobial activity, source of release material, adhesiveness, etc. Such properties may be imparted in substantially the entire web or at certain locations or portions of the web.

Suitable radiopaque materials include, for example, ceramics, mineralized bone, ceramics/calcium phosphate/calcium sulfate, metal particles, fibers, and iodinated polymers (see, e.g., WO 2007/143698). Polymeric materials can be used to form the mesh and to make it radiopaque by iodinating it, such as, for example, as taught in U.S. patent No. 6,585,755, which is incorporated herein by reference in its entirety. Other techniques for incorporating biocompatible metals or metal salts into polymers to increase the radiopacity of the polymer may also be used. Suitable antimicrobial materials may include, for example, trace metal elements. In some embodiments, trace metal elements may also promote bone growth.

In some embodiments, the web may comprise a material that becomes tacky when wetted. Such a material may be, for example, a protein or gelatin based material. Tissue adhesives, including mussel adhesive protein and cyanoacrylate, may be used to impart tack to the mesh. In other examples, alginate or chitosan materials may be used to impart tackiness to the mesh. In other embodiments, an adhesive substance or material may be placed on a portion of the mesh or in a particular area of the mesh to anchor that portion or area of the mesh in place at the implantation site.

Bone material

The bone material may be natural or synthetic bone material (e.g., tricalcium phosphate and/or hydroxyapatite). In various embodiments, the bone material may be in granular form, such as in the form of bone chips, powder, or fibers. If the bone is demineralized, the bone may be granulated before, during, or after demineralization. In some embodiments, the bone may be monolithic and may not be particulate.

Before or after demineralization, the bone may be ground and ground or otherwise processed into particles of appropriate size. The particles may be granular (e.g. powder) or fibrous. The term milling or grinding is not intended to be limited to the production of a particular type of particle and may refer to the production of granular or fibrous particles. In certain embodiments, the particle size may be greater than 25 microns, such as in the range of about 25 microns to about 2000 microns, or about 25 microns to about 500 microns, or about 200 microns to about 1000 microns. In some embodiments, the bone particles are less than 100 microns in size. In some embodiments, the bone particles are less than 500 microns in size.

After grinding, the bone particles may be sieved to select those particles of a desired size. In certain embodiments, the particles may be sieved through a 25 micron sieve, a 50 micron sieve, a 75 micron sieve, a 100 micron sieve, a 125 micron sieve, a 150 micron sieve, a 175 micron sieve, and/or a 200 micron sieve.

In some embodiments, the bone material comprises DBM and/or mineralized bone. In some embodiments, the bone material is less than 25 microns in size. In some embodiments, the bone material particle size is about 1 micron, 2 microns, 3 microns, 4 microns, 5 microns, 6 microns, 7 microns, 8 microns, 9 microns, 10 microns, 11 microns, 12 microns, 13 microns, 14 microns, 15 microns, 16 microns, 17 microns, 18 microns, 19 microns, 20 microns, 21 microns, 22 microns, 23 microns, 24 microns, and/or 25 microns.

In various embodiments, the bone meal, bone chips, and/or DBM and/or mineralized bone fibers have a tacky outer surface such that bone material may adhere to the DBM and/or mineralized bone fibers. In various embodiments, the bone meal is naturally sticky. In some embodiments, a binder is applied to the bone meal and/or bone fibers, the binder comprising a bioadhesive, an adhesive, a cement, a cyanoacrylate, a silicone, a hot melt adhesive, and/or a cellulosic binder. In various embodiments, the adhesive can be applied to the surface of the bone powder by spraying or brushing. In some embodiments, a charge is applied to the fibers and an opposite charge is applied to the bone meal (i.e., an electrostatic precipitation technique). The bone meal will be attracted and firmly adhere to the fiber surface. Any of these application techniques may be repeated one or more times to build up a relatively thick layer of adherent bone meal on the fiber surface.

The bone meal may be applied directly to the DBM fibers and/or fully mineralized fibers, chips and the mixture may be disposed in a web. In some embodiments, the bone material inserted into the mesh contains pores having a pore size of about 0.5 microns to about 2,000 microns. In some embodiments, the bone material inserted into the mesh contains pores having a pore size of about 0.5 microns, 5 microns, 50 microns, 100 microns, 150 microns, 200 microns, 250 microns, 300 microns, 350 microns, 400 microns, 450 microns, 500 microns, 550 microns, 600 microns, 650 microns, 700 microns, 750 microns, 800 microns, 850 microns, 900 microns, 950 microns, 1,000 microns, 1,050 microns, 1,100 microns, 1,150 microns, 1,200 microns, 1,250 microns, 1,300 microns, 1,350 microns, 1,400 microns, 1,450 microns, 1,500 microns, 1,550 microns, 1,600 microns, 1,650 microns, 1,700 microns, 1,750 microns, 1,800 microns, 1,850 microns, 1,900 microns, 1,950 microns to about 2,000 microns. In some embodiments, the pore size of the bone material is uniform. In some embodiments, the pore size of the bone material is non-uniform and includes various pore sizes in the range of 0.5 microns to about 2,000 microns. Alternatively, the DBM fibers, flakes, and DBM powder can be placed in a polymer (e.g., collagen) and inserted into a bone implant.

After shaving, milling, or other techniques to obtain them, the bone material is demineralized to reduce its inorganic content to very low levels, in some embodiments, to no more than about 5% by weight residual calcium and no more than about 1% by weight residual calcium. Demineralization of bone material typically causes it to shrink to some extent.

The bone used in the methods described herein may be autograft, allograft or xenograft. In various embodiments, the bone may be cortical bone, cancellous bone, or cortical-cancellous bone. Although specifically discussed herein with respect to demineralized bone matrix, bone matrix treated according to the teachings herein may be non-demineralized, partially demineralized, or surface demineralized. This discussion applies to demineralized, partially demineralized, and surface demineralized bone matrix. In one embodiment, the demineralized bone is derived from bovine bone or human bone. In another embodiment, the demineralized bone is derived from human bone. In one embodiment, the demineralized bone is derived from the patient's bone (autologous bone). In another embodiment, the demineralized bone is derived from a different animal (including cadavers) of the same species (allograft bone).

In some embodiments, the bone material may be patient autograft bone and another bone material such as, for example, an allograft, allograft DBM, a ceramic, and/or a combination of any of the foregoing bone materials. In some embodiments, the combined bone material may have a ratio of 50. In some embodiments, the combination bone material may have any ratio of.

In some embodiments, the bone material may be about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% to about 100% of patients autologous to about a patient graft bone or a combination thereof.

Any suitable means may be used to demineralize bone. Demineralization of bone material can be carried out according to known conventional procedures. For example, in a preferred demineralization procedure, bone material useful in the implantable compositions of the present application is subjected to an acid demineralization step followed by a degreasing/sterilization step. The bone material is immersed in acid, which demineralizes it over time. Acids that may be used in this step include inorganic acids such as hydrochloric acid; and organic acids such as peracetic acid, acetic acid, citric acid, or propionic acid. The depth of demineralization into the bone surface can be controlled by adjusting the treatment time, the temperature of the demineralization solution, the concentration of the demineralization solution, the intensity of agitation during treatment, and other applied forces, such as vacuum, centrifuge, pressure, and other factors as known to those skilled in the art. Thus, in various embodiments, the bone material may be fully demineralized, partially demineralized, or surface demineralized.

After acid treatment, the bone is rinsed with sterile water for injection, buffered to a final predetermined pH value with a buffer, and then finally rinsed with water for injection to remove residual amounts of acid and buffer or washed with water to remove residual acid and thereby increase the pH. After demineralization, the bone material is immersed in the solution to degrease it. The degreasing/disinfectant solution is an aqueous solution of ethanol, which is a good solvent for lipids, and water, which is a good hydrophilic vehicle to allow the solution to penetrate deeper into bone. Aqueous ethanol solutions also disinfect bone by killing vegetative microbes and viruses. Generally, at least about 10 to 40 weight percent water (i.e., about 60 to 90 weight percent of a degreasing agent, such as ethanol) should be present in the degreasing/sanitizing solution to achieve optimal lipid removal and sanitizing in a minimum amount of time. The concentration of the degreasing solution ranges from about 60 to 85 wt% ethanol or about 70 wt% ethanol.

In addition, according to the present application, the DBM material may be used immediately for preparing the bone implant, or it may be stored under sterile conditions, advantageously in a critical point dry state prior to such preparation. In one embodiment, the bone material may retain some of its original mineral content, such that the composition can be imaged using radiographic techniques.

In various embodiments, the present application also provides bone matrix compositions comprising Critical Point Drying (CPD) fibers. DBM comprises a collagen matrix of bone and acid insoluble proteins, including Bone Morphogenic Protein (BMP) and other growth factors. The DBM can be formulated for use as a microparticle, pellet, sphere, gel, sponge, or putty, and can be freeze dried for storage. Sterilization procedures used to prevent disease transmission may reduce the activity of beneficial growth factors in DBM. The DBM provides an initial osteoconductive matrix and exhibits a certain degree of osteoinductive potential, inducing infiltration and differentiation of osteoprogenitor cells from surrounding tissues.

DBM formulations have been used in orthopedic medicine for many years to promote bone formation. For example, DBM has been found to be useful in repairing bone fractures, fusing vertebrae, joint replacement surgery, and treating bone destruction due to potential diseases such as rheumatoid arthritis. DBM is thought to promote bone formation in vivo through osteoconductive and osteoinductive processes. Osteoinductive effects of the implanted DBM composition are believed to be caused by the presence of active growth factors present on the isolated collagen-based matrix. These factors comprise members of the TGF- β, IGF, and BMP protein families. Examples of osteoinductive factors include TGF- β, IGF-1, IGF-2, BMP-7, parathyroid hormone (PTH), and angiogenic factors. Other osteoinductive factors, such as osteocalcin and osteopontin, may also be present in the DBM formulation. Other unnamed or undiscovered osteoinductive factors may also be present in the DBM.

In various embodiments, the DBM provided in the kits, implants, and methods described herein is prepared from elongated bone fibers that have undergone Critical Point Drying (CPD). The elongated CPD bone fibers used in the present application are generally characterized as having a relatively high average length to average width ratio, also referred to as aspect ratio. In various embodiments, the elongated bone fibers have an aspect ratio of at least about 50. Such elongated bone fibers may be readily obtained by any of several methods, such as by abrading or cutting the entire bone or a relatively large portion of the surface of the bone.

In other embodiments, the fibers may have a length of at least about 3.5cm and an average width of from about 20mm to about 1cm. In various embodiments, the elongated fibers may have an average length of about 3.5cm to about 6.0cm and an average width of about 20mm to about 1cm. In other embodiments, the elongated fibers may have an average length of about 4.0cm to about 6.0cm and an average width of about 20mm to about 1cm.

In other embodiments, the diameter or average width of the elongated fibers is, for example, no greater than about 1.00cm, no greater than 0.5cm, or no greater than about 0.01cm. In other embodiments, the diameter or average width of the fibers may be from about 0.01cm to about 0.4cm or from about 0.02cm to about 0.3cm.

In another embodiment, the aspect ratio of the fiber can be from about 50; or about 50. The aspect ratio of the fiber according to the present disclosure can be from about 50.

In some embodiments, the chip to fiber ratio is about 90. In various embodiments, the surface demineralization chip to fiber ratio is from about 90, 80, 20, 75, 25, 70. In some embodiments, the surface demineralized chips to fully demineralized fibers ratio is about 90.

In some embodiments, the DBM fiber has a thickness of about 0.5mm to 4 mm. In various embodiments, the DBM fiber has a thickness of about 0.5mm, 0.6mm, 0.7mm, 0.8mm, 0.9mm, 1mm, 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, and/or 4 mm. In various embodiments, the ratio of DBM fiber to DBM powder is from about 40 to about 90. In some embodiments, the ratio of mineralized bone fibers to DBM powder is from about 25 to about 75. In various embodiments, the bone implant comprises DBM fibers and mineralized fibers in a ratio of 40 to about 90. In some embodiments, the DBM fiber to DBM powder ratio, the mineralized bone fiber to DBM powder ratio, and/or the DBM fiber to mineralized fiber ratio is from 5. In some embodiments, the DBM fiber to DBM powder ratio, mineralized bone fiber to DBM powder ratio, and/or DBM fiber to mineralized fiber ratio is 5.

In some embodiments, the bone material comprises demineralized bone material comprising demineralized bone, fibers, powder, chips, triangular prisms, spheres, cubes, cylinders, chips, or other shapes having irregular or random geometries. These may comprise, for example, "substantially demineralized", "partially demineralized" or "fully demineralized" cortical and/or cancellous bone. These also comprise surface demineralization, wherein the surfaces of the bone structures are substantially demineralized, partially demineralized, or fully demineralized, while the bulk of the bone structures are fully mineralized.

In various embodiments, the bone material comprises fully DBM fibers and surface demineralized bone chips. In some embodiments, the ratio of complete DBM fibers to surface demineralized bone chips is from 5. In some embodiments, the ratio of complete DBM fiber to surface demineralized bone chips is 5. In various embodiments, the complete DBM fiber has a thickness of about 0.5 to 4 mm. In various embodiments, the complete DBM fiber has a thickness of about 0.5mm, 0.6mm, 0.7mm, 0.8mm, 0.9mm, 1mm, 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, and/or 4 mm.

In various embodiments, the fiber and/or powder is surface DBM. In some embodiments, the fibers and/or powder are surface DBM cortical allografts. In various embodiments, surface demineralization involves surface demineralization of at least a certain depth. For example, the surface demineralization of the allograft may be from about 0.25mm, 0.5mm, 1mm, 1.5mm, 2.0mm, 2.5mm, 3.0mm, 3.5mm, 4mm, 4.5mm to about 5mm. The edges of the bone fibers and/or powder may be further machined to any shape or contain features such as grooves, protrusions, depressions, etc. to help improve fit and limit any movement or micromotion to help the fusion and/or osteoinduction occur.

The DBM is typically dried, for example by freeze drying or solvent drying, to store and maintain the DBM in an active condition for implantation. In addition, each of these procedures is believed to reduce the overall surface area structure of the bone. It is appreciated that structural damage to the outer surface reduces the overall surface area. Physical changes to the surface and reduction in surface area may affect cell attachment, migration, proliferation and differentiation. The affinity of the surface for growth factors and the kinetics of release of growth factors from the surface may also be altered.

Thus, in some embodiments, methods are provided for drying bone to store and maintain the bone in an active condition for implantation that maintains or increases the surface area of the bone. In one embodiment, the bone matrix is treated using a Critical Point Drying (CPD) technique, thereby reducing disruption of the bone surface. While critical point drying is specifically described, it is to be understood that in alternative embodiments, supercritical point processing may be used. In various embodiments utilizing CPD, the percentage of collagen fibrils on the bone surface after drying are not denatured to a residual moisture content of about 15% or less. In some embodiments, the bone matrix has a residual moisture content of about 8% or less after drying. In some embodiments, the bone matrix has a residual moisture content of about 6% or less after drying. In some embodiments, the bone matrix has a residual moisture content of about 3% or less after drying.

Evaporative drying and freeze-drying of the sample may deform and collapse the surface structure, thereby reducing the surface area. Without wishing to be bound by a particular theory, it is believed that this deformation and structure occurs because as a substance passes through the boundary from liquid to gas, the substance volatizes such that the volume of the liquid decreases. When this occurs, surface tension at the solid-liquid interface can pull any structure to which the liquid is attached. This surface tension tends to break up the fine surface structure. This damage may be caused by the effect of surface tension on the liquid/gas interface. Critical point drying is a technique that avoids the effects of surface tension on the liquid/gas interface by substantially preventing the liquid/gas interface from occurring. The critical point or supercritical drying does not cross any phase boundary but rather passes through the supercritical region where the distinction between gas and liquid no longer applies. Thus, materials dehydrated using critical point drying are not subject to destructive surface tension. When the critical point of the liquid is reached, it is possible to switch from liquid to gas without sudden state changes. Critical point drying can be used with bone matrix for phase change from liquid to dry gas without being affected by surface tension. Thus, drying dehydrated bone using critical points may preserve or increase at least some surface structure and thus surface area.

In some embodiments, critical point drying is performed using carbon dioxide. However, other media such as Freon (Freon), including Freon 13 (chlorotrifluoromethane) may be used. Typically, fluids suitable for supercritical drying comprise carbon dioxide (critical point is 304.25K at 7.39MPa or 31.1 deg.C or 31.2 deg.C and 73.8 bar at 1072 psi) and Freon (about 300K at 3.5-4MPa or 25-30 deg.C at 500-600 psi). Nitrous oxide has similar physical behavior to carbon dioxide, but is a potent oxidant in its supercritical state. Supercritical water is also a powerful oxidant, in part because its critical point occurs at such high temperatures (374 ℃) and pressures (3212 psi/647K and 22.064 MPa).

In some embodiments, the bone may be pretreated to remove water prior to critical point drying. Thus, according to one embodiment, carbon dioxide is used to dry the bone matrix at (or above) its critical point state. After demineralization, the bone matrix sample may be dehydrated (in water) to remove residual water content. Such dehydration can be achieved, for example, by using a series of graded ethanol solutions (e.g., deionized water containing 20%, 50%, 70%, 80%, 90%, 95%, 100% ethanol). In some embodiments, the infiltration of the tissue with a gradient series of ethanol solutions or alcohols can be accomplished in an automated fashion. For example, pressure and vacuum may be used to accelerate penetration into tissue.

External member

In some embodiments, a device is provided that retains a mesh while it is being rolled to at least partially encapsulate a bone material. The device may be a tray and may be positioned in an upright configuration during placement of bone material into the mesh. The tray may be a thermoformed tray including a central slot. The tray may or may not be part of the sterile packaging for the bone implant. The tray may also include protrusions or other features to grip and/or retain the bone implant in a desired spatial arrangement. Suitable trays for filling coverings (e.g., mesh) with bone material are described in U.S. patent publication 20180311049 to Shimko et al (U.S. serial No. 15/581817, filed on 28.4.2017) and U.S. patent publication 20190021862 to Kalpakci et al (U.S. serial No. 15/656112, filed on 21.7.2017). The entire disclosures of these applications are incorporated herein by reference.

In various aspects, a kit is provided that includes a bone implant 10 as described herein, including a covering 18, which in some aspects may be a mesh 32 configured to be rolled to a diameter to at least partially encapsulate a bone material 12. The kit may further comprise at least one of: a plurality of sizing rings 44, or a plurality of sizing cylinders 46, or one or more funnels 48 of different diameters, or funnels 50 of varying diameters. A plurality of rings or a plurality of sizing cylinders are configured to engage the bone implant to adapt the implant to a desired diameter. One or more funnels, including a variable diameter funnel, are configured to load covering 18 with a quantity of bone material. In some embodiments, the kit includes a separate closure member 24, e.g., a bone suture. In various embodiments, as described above, the closure member may be one or more strands 42 attached to the mesh 32.

In some embodiments, the mesh may be provided in a rolled configuration, and sizing cylinder 46 may be used to fill the rolled mesh. In this manner, a predetermined amount of bone material may be added to one or more sizing cylinders to load a desired amount of bone material into the mesh. This can also be achieved with a variable diameter funnel.

The kit may also include bone material, such as demineralized bone matrix, allograft, xenograft, ceramic, or mixtures thereof. In various aspects, the kit can include a tray 70 as shown in fig. 11.

In some embodiments, the kit may further comprise a desiccant to prevent hydrolytic degradation during storage. Useful desiccants for the kits described herein include, but are not limited to, sachets that encapsulate silica gel, clay, activated carbon, calcium sulfate, calcium chloride, and molecular sieves (e.g., zeolites), among others.

In other embodiments, a kit for manufacturing a bone implant is provided, wherein the kit comprises: a covering comprising a body portion and a closure portion adjacent the body portion, the closure portion configured to hold the covering in a rolled configuration to a predetermined diameter to at least partially encapsulate bone material; and a binder. In some embodiments, the cover provided in the kit is prepared by 3D printing.

The kit may be used with a bone implant configured for minimally invasive midline lumbar fusion, posterior cervical fusion, and oromaxillofacial revision surgery. The kit may also be used with bone implants for: healing vertebral compression fractures, interbody fusion, additional minimally invasive surgery, posterolateral fusion surgery, correction of adult or pediatric scoliosis, treatment of long bone defects, osteochondral defects, crest augmentation (dental/craniomaxillofacial, e.g., edentulous patients), trauma plate-down, tibial plateau defects, filling bone cysts, wound healing, peritraumatic, plastic (cosmetic/plastic/reconstructive surgery), and the like.

The tray may be made of metal, thermoformed material, or polymers such as polyurethane, polyurea, polyether (amide), PEBA, thermoplastic elastomeric olefins, copolyesters, and styrenic thermoplastic elastomers, steel, aluminum, stainless steel, titanium, nitinol, metal alloys with high non-ferrous metal content and low relative iron content, carbon fiber, fiberglass, plastic, ceramic, or combinations thereof.

When the tray is made of a thermoformable material, the thermoformable material may be Acrylonitrile Butadiene Styrene (ABS), polymethyl methacrylate (PMMA, acrylic or Acrylic)

) High Density Polyethylene (HDPE), high Impact Polystyrene (HIPS), KYDEXTM (PMMA/polyvinyl chloride (PVC) blend), polycarbonate (PC), polyetherimide (PEI or PEI)

) Polyethylene terephthalate glycol (PETG), polypropylene (PP), polyvinyl chloride (PVC), thermoplastic Polyolefin (TPO).

The tray may also be made of shape memory polymers including, but not limited to, polyethers, polyacrylates, polyamides, polysiloxanes, polyurethanes, polyetheramides, polyurethane/ureas, polyetheresters, polynorbornenes, cross-linked polymers (e.g., cross-linked polyethylene and cross-linked poly (cyclooctene)), hybrid inorganic-organic polymers, and copolymers, such as urethane/butadiene copolymers, styrene-butadiene copolymers. Memory shape alloys include, but are not limited to, tiNi, cuZnAl, and FeNiAl alloys.

In some embodiments, the tray may include visual indicia, such as, for example, a flag that enables a user to measure a defined volume of material placed into the web. In some embodiments, the tray may include length and/or volume markings that aid in filling the web.

In various embodiments, the kit may include additional components, such as a scraper, a mixing bowl, a wiper, a needle, a measuring device, and a syringe, along with the bone implant and the tray. The kit may include a mesh in the first compartment. The second compartment may include a vial containing bone material, diluent, and any other instrumentation necessary for local implant delivery. The third compartment may comprise a tray for filling the bone implant. The fourth compartment may include gloves, drapes, wound dressings, and other surgical supplies for maintaining sterility of the implantation process, as well as a brochure that may include a chart showing how the bone implant is implanted. The fifth compartment may include additional needles, measuring devices, fasteners, and/or sutures. Each tool can be individually packaged in a radiation sterilized plastic pouch. The sixth compartment may contain a pharmaceutical agent for radiographic imaging. The lid of the kit may contain instructions for the implantation procedure and a clear plastic lid may be placed over the compartment to maintain sterility.

Method of use

A method of implanting a bone implant at a surgical site beneath the skin of a patient is provided. The method comprises the following steps: providing a bone implant 10 comprising a cover 18 configured to be rolled to a diameter D to encapsulate bone material 12 at least within the cover; encapsulating the bone material in the covering by adapting the covering to a rolled configuration; and placing the bone implant at the surgical site, thereby implanting the bone implant at the surgical site. The bone implant implanted by this method may be, for example, the bone implant 10 shown in fig. 1-3, 4A, 4B, 5A, 5B, 6, and 7A-7E. The implantation sites correspond to minimally invasive midline lumbar fusion, posterior cervical fusion and oral maxillofacial repair surgery. In many aspects, the bone material can be fully demineralized bone fibers and surface demineralized bone fragments. The implantation site may also correspond to healing vertebral compression fractures, interbody fusion, additional minimally invasive surgery, posterolateral fusion surgery, correction of adult or pediatric scoliosis, treatment of long bone defects, osteochondral defects, crest augmentation (dental/craniomaxillary, e.g., edentulous patients), trauma plate-down, tibial plateau defects, filling of bone cysts, wound healing, peritraumatic, shaping (cosmetic/plastic/reconstructive surgery), and the like.

The method may also be used for surgical treatments where the patient is in a prone or supine position, and/or various surgical approaches are employed to the spine and in other body regions, including anterior, posterior midline, anterolateral, and/or anterior approaches. The method may also be used with procedures for treating the lumbar, cervical, thoracic, sacral and pelvic regions of the spine. The method may also be used on animals, bone models and other inanimate substrates, for example in training, testing and demonstration.

In some embodiments, the ends of the bone implant may be sealed manually by the user, as shown in fig. 2, using

adhesive

26, 28 or surgical sutures at either end of the rolled covering. The mesh may alternatively be rolled by the user to encapsulate or partially encapsulate the bone material into the bone implant.

In some embodiments, the bone implant may be used for healing vertebral compression fractures, interbody fusion, minimally invasive surgery, posterolateral fusion, adult or pediatric scoliosis correction, treatment of long bone defects, osteochondral defects, crest augmentation (dental/craniomaxillofacial, e.g., edentulous patients), below wound plates, tibial plateau defects, filling bone cysts, wound healing, periwound, reshaping (cosmetic/plastic/reconstructive surgery), and the like. Bone implants may be used for minimally invasive surgery via placement through a small incision or other means. The size and shape can be designed to limit the transport conditions.

Generally, the bone implant can be applied to a pre-existing defect, formed passage, or modified defect. Thus, for example, a channel can be formed in a bone, or a preexisting defect can be cut to form a channel to receive a bone implant. The bone implant can be configured to fit a passage or defect. In some embodiments, the configuration of the bone implant can be selected to match the passage. In other embodiments, a channel may be created or the defect expanded or altered to reflect the configuration of the bone implant. A bone implant can be placed in the defect or passage and optionally coupled using an attachment mechanism.

In some embodiments, the bone implants of the present application can provide a bone material (e.g., DBM) in a dry form that is free of a carrier (water, saline, blood, glycerol, etc.). Alternatively, the bone material may be hydrated with blood, saline, water, glucose, or the like at the point of care to form a wet material before, during, or after it is encapsulated in the covering and implanted.

Although the present invention has been described with reference to embodiments, workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention.

Claims

1. A bone implant for encapsulating bone material, the bone implant comprising a cover comprising a body portion and a closure portion adjacent the body portion, the closure portion configured to hold the cover in a rolled configuration to a predetermined diameter to at least partially encapsulate the bone material.

2. A bone implant according to claim 1, wherein the covering is biodegradable and includes a mesh.

3. A bone implant according to claim 1, wherein the body portion includes lines having a narrower regular pattern and the closure portion includes lines having a wider regular pattern relative to the body portion to at least partially encapsulate the bone material.

4. A bone implant according to claim 3, wherein the closure portion is (i) more flexible than the body portion or (ii) more deformable than the body portion.

5. A bone implant according to claim 1, wherein the closure portion maintains the cover in a rolled configuration without reducing porosity of the body portion.

6. A bone implant according to claim 1, wherein the covering includes a biodegradable mesh having a shape memory to allow positioning from a planar configuration to a coiled configuration to at least partially encapsulate the bone material.

7. A bone implant according to claim 2, wherein the mesh includes at least one or more of: poly (lactide-co-glycolide) (PLGA), polylactide (PLA), polyglycolide (PGA), D-lactide, D, L-lactide, D, L-lactide-co-epsilon-caprolactone, D, L-lactide-co-glycolide-co-epsilon-caprolactone, poly (D, L-lactide-co-caprolactone), poly (D, L-lactide), poly (D-lactide), poly (L-lactide), poly (ester amide), hydroxyapatite, calcium phosphate, ceramic, or a combination thereof.

8. A bone implant according to claim 2, wherein the bone material is completely encapsulated by the mesh, and the mesh is porous to allow cellular influx and efflux.

9. A bone implant according to claim 2, wherein the mesh further includes a polymer coating, the coating including a bioactive agent.

10. A bone implant according to claim 9, wherein the bioactive agent includes osteogenic or chondrogenic proteins or peptides, demineralized bone matrix powder, growth factors, antibiotics, drugs, or combinations thereof.

11. A bone implant according to claim 2, wherein (i) the mesh includes an inner portion and an outer portion, all or a portion of the inner portion and/or the outer portion including an adhesive material disposed thereon; or (ii) the mesh comprises an inner portion and an outer portion, a portion of the inner portion and/or the outer portion having a mating surface configured to retain the mesh in the rolled configuration.

12. A bone implant according to claim 11, wherein a first mating surface includes a protrusion or hook and a second mating surface includes a mating void for retaining the mesh in the rolled configuration.

13. A bone implant according to claim 11, wherein (i) the adhesive material is water-activated; (ii) the adhesive material is applied at the time of use; (iii) The binder material comprises a volatile solvent which, upon evaporation, renders the web tacky to provide self-adhesion.

14. A bone implant according to claim 11, wherein the inner or outer portion of the mesh has a plurality of spaced apart indicia to assist in sizing the covering for implantation.

15. A kit for manufacturing a bone implant, the kit comprising: a covering comprising a body portion and a closure portion adjacent the body portion, the closure portion configured to hold the covering in a rolled configuration to a predetermined diameter to at least partially encapsulate the bone material; and a package for containing the cover.

16. The kit of claim 15, further comprising bone material comprising demineralized bone matrix, allograft, xenograft, ceramic, or a combination thereof.

17. The kit of claim 16, further comprising a tray for holding the mesh to facilitate positioning of the bone material into the rolled mesh; and a binder.

18. The kit of claim 15, wherein the overlay is prepared by 3D printing.

19. A method of implanting a bone implant at a surgical site, the method comprising: providing a bone implant comprising a cover comprising a body portion and a closure portion adjacent the body portion, the closure portion configured to hold the cover in a rolled configuration to a predetermined diameter to at least partially encapsulate the bone material; encapsulating the bone material in the covering by adapting the covering to a rolled configuration; and placing the bone implant at the surgical site, thereby implanting the bone implant at the surgical site.

20. The method of claim 19, wherein the bone material is demineralized bone matrix, allograft, xenograft, ceramic, or a combination thereof.